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Emanuilov AI, Budnik AF, Masliukov PM. Somatostatin-immunoreactive neurons of the rat gut during the development. Histochem Cell Biol 2024; 162:385-402. [PMID: 39153131 DOI: 10.1007/s00418-024-02322-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/11/2024] [Indexed: 08/19/2024]
Abstract
Somatostatin (SST) is a peptide expressed in the peripheral and central nervous systems, as well as in endocrine and immune cells. The aim of the current study is to determine the percentage of SST immunoreactive (IR) neurons and their colocalization with choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), neuropeptide Y (NPY), and glial fibrillary acidic protein (GFAP) in the myenteric plexus (MP) and submucous plexus (SP) of the small intestine (SI) and large intestine (LI) of rats across different age groups from newborn to senescence using immunohistochemistry. In the MP of the SI and LI, the percentage of SST-IR neurons significantly increased during early postnatal development from 12 ± 2.4 (SI) and 13 ± 3.0 (LI) in newborn rats to 23 ± 1.5 (SI) and 18 ± 1.6 (LI) in 20-day-old animals, remaining stable until 60 days of age. The proportion of SST-IR cells then decreased in aged 2-year-old animals to 14 ± 2.0 (SI) and 10 ± 2.6 (LI). In the SP, the percentage of SST-IR neurons significantly rose from 22 ± 3.2 (SI) and 23 ± 1.7 (LI) in newborn rats to 42 ± 4.0 in 20-day-old animals (SI) and 32 ± 4.9 in 30-day-old animals (LI), before declining in aged 2-year-old animals to 21 ± 2.6 (SI) and 28 ± 7.4 (LI). Between birth and 60 days of age, 97-98% of SST-IR neurons in the MP and SP colocalized with ChAT in both plexuses of the SI and LI. The percentage of SST/ChAT neurons decreased in old rats to 85 ± 5.0 (SI) and 90 ± 3.8 (LI) in the MP and 89 ± 3.2 (SI) and 89 ± 1.6 (LI) in the SP. Conversely, in young rats, only a few SST-IR neurons colocalized with nNOS, but this percentage significantly increased in 2-year-old rats. The percentage of SST/NPY-IR neurons exhibited considerable variation throughout postnatal development, with no significant differences across different age groups in both the MP and SP of both intestines. No colocalization of SST with GFAP was observed in any of the studied animals. In conclusion, the expression of SST in enteric neurons increases in young rats and decreases in senescence, accompanied by changes in SST colocalization with ChAT and nNOS.
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Affiliation(s)
- Andrey I Emanuilov
- Department of Human Anatomy, Yaroslavl State Medical University, Yaroslavl, Russia
| | - Antonina F Budnik
- Department of Normal and Pathological Anatomy, Kabardino-Balkarian State University Named After H.M. Berbekov, Nalchik, Russia
| | - Petr M Masliukov
- Department of Human Anatomy, Yaroslavl State Medical University, Yaroslavl, Russia.
- Department of Normal Physiology and Biophysics, Yaroslavl State Medical University, Revoliucionnaya 5, Yaroslavl, Russia, 150000.
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Budnik AF, Aryaeva D, Vyshnyakova P, Masliukov PM. Age related changes of neuropeptide Y-ergic system in the rat duodenum. Neuropeptides 2020; 80:101982. [PMID: 31708113 DOI: 10.1016/j.npep.2019.101982] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 11/02/2019] [Accepted: 11/04/2019] [Indexed: 12/31/2022]
Abstract
Neuropeptide Y (NPY) is widely distributed in the autonomic nervous system and acts as a neurotransmitter and a trophic factor. However, there is no report concerning the expression of NPY and its receptors in the intestine during postnatal ontogenesis. In the current study, immunohistochemistry and western blot analysis was used to label NPY, Y1R, Y2R and Y5R receptors in the duodenum from rats of different ages (1-, 10-, 20-, 30-, 60-day-old and 2-year-old). The obtained data suggest age-dependent changes of NPY-mediated gut innervation. NPY-immunoreactive (IR) neurons were observed in the myenteric (MP) and submucous (SP) plexus from the moment of birth. In the MP, the percentage of NPY-IR neurons was low and varied from 4.1 ± 0.32 in 1-day-old to 2.9 ± 0.62 in 2-year-old rats. The proportion of NPY-IR myenteric neurons did not change significantly through the senescence (p > .05). In the SP, the proportion of NPY-IR neurons significantly increased in the first month of life from 56.3 ± 2.4% in 1-day-old to 78.1 ± 5.18% in 20-day-old and significantly decreased from 75.6 ± 4.62% in 30-day-old rats to 59.8 ± 4.24% in 2-year-old rats. The expression of NPY in the duodenum did not change significantly during the development by western blot analysis. The expression of Y1R and Y2R was low in newborns and upregulated in the first ten days of life. The expression of Y5R was maximal in newborn pups and significantly decreased in in the first 20 days. Thus, there are some fluctuation of the percentage of NPY-IR neurons accompanies changes in relation of different subtypes of NPY receptors in the small intestine during postnatal ontogenesis.
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Affiliation(s)
- Antonina F Budnik
- Department of Normal and Pathological Anatomy, Kabardino-Balkarian State University named after H.M. Berbekov, Nalchik, Russia
| | - Daria Aryaeva
- Department of Normal Physiology, Yaroslavl State Medical University, Yaroslavl, Russia
| | - Polina Vyshnyakova
- Department of Normal Physiology, Yaroslavl State Medical University, Yaroslavl, Russia
| | - Petr M Masliukov
- Department of Normal Physiology, Yaroslavl State Medical University, Yaroslavl, Russia; Petrozavodsk State University, Petrozavodsk, Russia.
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Gonkowski S, Rytel L. Somatostatin as an Active Substance in the Mammalian Enteric Nervous System. Int J Mol Sci 2019; 20:ijms20184461. [PMID: 31510021 PMCID: PMC6769505 DOI: 10.3390/ijms20184461] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 08/22/2019] [Accepted: 09/08/2019] [Indexed: 12/12/2022] Open
Abstract
Somatostatin (SOM) is an active substance which most commonly occurs in endocrine cells, as well as in the central and peripheral nervous system. One of the parts of the nervous system where the presence of SOM has been confirmed is the enteric nervous system (ENS), located in the wall of the gastrointestinal (GI) tract. It regulates most of the functions of the stomach and intestine and it is characterized by complex organization and a high degree of independence from the central nervous system. SOM has been described in the ENS of numerous mammal species and its main functions in the GI tract are connected with the inhibition of the intestinal motility and secretory activity. Moreover, SOM participates in sensory and pain stimuli conduction, modulation of the release of other neuronal factors, and regulation of blood flow in the intestinal vessels. This peptide is also involved in the pathological processes in the GI tract and is known as an anti-inflammatory agent. This paper, which focuses primarily on the distribution of SOM in the ENS and extrinsic intestinal innervation in various mammalian species, is a review of studies concerning this issue published from 1973 to the present.
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Affiliation(s)
- Slawomir Gonkowski
- Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowski Str. 13, 10-718 Olsztyn, Poland.
| | - Liliana Rytel
- Department and Clinic of Internal Diseases, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowski Str. 14, 10-718 Olsztyn, Poland.
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Chen FX, Yu YB, Yuan XM, Zuo XL, Li YQ. Brain-derived neurotrophic factor enhances the contraction of intestinal muscle strips induced by SP and CGRP in mice. REGULATORY PEPTIDES 2012; 178:86-94. [PMID: 22800960 DOI: 10.1016/j.regpep.2012.07.001] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2011] [Revised: 06/08/2012] [Accepted: 07/06/2012] [Indexed: 01/13/2023]
Abstract
BACKGROUND AND AIMS Brain-derived neurotrophic factor (BDNF) has been found in the intestinal tract of a variety of species. Its effects on visceral hyperalgesia have been examined to some degree, but limited studies have focused on gut motility. The aim of the present study was to investigate the effects of BDNF on gut motility of mice. METHODS Longitudinal muscle (LM) strips were prepared from mice ileum and distal colon. The motility of gut was evaluated by the contraction of LM strips, which was recorded by a polyphisograph in vitro. Firstly, the roles of substance P (SP), calcitonin gene-related peptide (CGRP), and acetylcholine (ACh) on the contraction of LM strips were clarified. Then the exogenous BDNF was administered, and the alterations of SP/CGRP/ACh-induced contractions of the muscle strips were explored. Finally, heterozygous BDNF(+/-) mice and antibody of TrkB were introduced to investigate the role of endogenous BDNF on the SP/CGRP/ACh-induced gut motility. KEY RESULTS SP (10(-8)-10(-6) mol L(-1)), CGRP (10(-8)-10(-7) mol L(-1)) and ACh (10(-8)-10(-6) mol L(-1)) dose-dependently caused the contraction of LM strips from ileum and distal colon, while the excitatory effect of CGRP was preceded by a transient inhibition. But 10(-6) mol L(-1) CGRP inhibited the contraction of LM strips. Pretreatment with exogenous BDNF (10(-8) mol L(-1)) remarkably enhanced the contraction of LM strips induced by SP (10(-9)-10(-7) mol L(-1)) and CGRP (10(-8)-10(-9) mol L(-1)). However, exogenous BDNF couldn't affect the contraction induced by ACh (10(-9)-10(-7) mol L(-1)). The excitatory effects of SP (10(-8)-10(-6) mol L(-1)) and CGRP (10(-8)-10(-7) mol L(-1)) on the contractions of LM strips from ileum and distal colon were significantly attenuated in BDNF(+/-) mice compared with those in BDNF(+/+) mice, while no difference of the effects of ACh (10(-8)-10(-6) mol L(-1)) on LM strips was observed between BDNF(+/-) mice and BDNF(+/+) mice. The monoclonal antibody of TrkB (TrkB-Ab) dramatically attenuated the excitatory effects of SP and CGRP on the contractions of LM strips, without affecting the excitatory effects of ACh. CONCLUSIONS AND INFERENCES These data clarified the excitatory effects of SP, ACh and bilateral effects of CGRP on gut motility of mice and confirmed an essential role of BDNF on accelerating gut motility by enhancing the excitatory effects of SP/CGRP.
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Affiliation(s)
- Fei-xue Chen
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, PR China
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Abstract
Intestinal inflammation is controlled by various immunomodulating cells, interacting by molecular mediators. Neuropeptides, released by enteric nerve cells and neuroendocrine mucosa cells, are able to affect several aspects of the general and intestinal immune system, with both pro- as well as anti-inflammatory activities. In inflammatory bowel disease (IBD) there is both morphological as well as experimental evidence for involvement of neuropeptides in the pathogenesis. Somatostatin is the main inhibitory peptide in inflammatory processes, and its possible role in IBD is discussed.
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Affiliation(s)
- J D van Bergeijk
- Department of Gastroenterology/Internal Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands
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Immunohistochemical analysis of substance P-containing neurons in rat small intestine. Cell Tissue Res 2010; 343:331-41. [DOI: 10.1007/s00441-010-1080-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2010] [Accepted: 10/18/2010] [Indexed: 10/18/2022]
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Phillips RJ, Pairitz JC, Powley TL. Age-related neuronal loss in the submucosal plexus of the colon of Fischer 344 rats. Neurobiol Aging 2007; 28:1124-37. [DOI: 10.1016/j.neurobiolaging.2006.05.019] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2005] [Revised: 03/07/2006] [Accepted: 05/10/2006] [Indexed: 11/28/2022]
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Hang CH, Shi JX, Li JS, Wu W, Li WQ, Yin HX. Levels of vasoactive intestinal peptide, cholecystokinin and calcitonin gene-related peptide in plasma and jejunum of rats following traumatic brain injury and underlying significance in gastrointestinal dysfunction. World J Gastroenterol 2004; 10:875-80. [PMID: 15040036 PMCID: PMC4727008 DOI: 10.3748/wjg.v10.i6.875] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To study the alterations of brain-gut peptides following traumatic brain injury (TBI) and to explore the underlying significance of these peptides in the complicated gastrointestinal dysfunction.
METHODS: Rat models of focal traumatic brain injury were established by impact insult method, and divided into 6 groups (6 rats each group) including control group with sham operation and TBI groups at postinjury 3, 12, 24, 72 h, and d 7. Blood and proximal jejunum samples were taken at time point of each group and gross observations of gastrointestinal pathology were recorded simultaneously. The levels of vasoactive intestinal peptide (VIP) in plasma, calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK) in both plasma and jejunum were measured by enzyme immunoassay (EIA). Radioimmunoassay (RIA) was used to determine the levels of VIP in jejunum.
RESULTS: Gastric distension, delayed gastric emptying and intestinal dilatation with a large amount of yellowish effusion and thin edematous wall were found in TBI rats through 12 h and 72 h, which peaked at postinjury 72 h. As compared with that of control group (247.8 ± 29.5 ng/L), plasma VIP levels were significantly decreased at postinjury 3, 12 and 24 h (106.7 ± 34.1 ng/L, 148.7 ± 22.8 ng/L, 132.8 ± 21.6 ng/L, respectively), but significantly increased at 72 h (405.0 ± 29.8 ng/L) and markedly declined on d 7 (130.7 ± 19.3 ng/L). However, Plasma levels CCK and CGRP were significantly increased through 3 h and 7 d following TBI (126-691% increases), with the peak at 72 h. Compared with control (VIP, 13.6 ± 1.4 ng /g; CGRP, 70.6 ± 17.7 ng/g); VIP and CGRP levels in jejunum were significantly increased at 3 h after TBI (VIP, 35.4 ± 5.0 ng/g; CGRP, 103.8 ± 22.1 ng/g), and declined gradually at 12 h and 24 h (VIP, 16.5 ± 1.8 ng/g, 5.5 ± 1.4 ng/g; CGRP, 34.9 ± 9.7 ng/g, 18.5 ± 7.7 ng/g), but were significantly increased again at 72 h (VIP, 48.7 ± 9.5 ng/g; CGRP, 142.1 ± 24.3 ng/g), then declined in various degrees on d 7 (VIP, 3.8 ± 1.1 ng/g; CGRP, 102.5 ± 18.1 ng/g). The CCK levels in jejunum were found to change in a similar trend as that in plasma with the concentrations of CCK significantly increased following TBI (99-517% increases) and peaked at 72 h.
CONCLUSION: Traumatic brain injury can lead to significant changes of brain-gut peptides in both plasma and small intestine, which may be involved in the pathogenesis of complicated gastrointestinal dysfunction.
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Affiliation(s)
- Chun-Hua Hang
- Department of Neurosurgery, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
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Abstract
Neurotrophin-3 (NT-3) promotes enteric neuronal development in vitro; nevertheless, an enteric nervous system (ENS) is present in mice lacking NT-3 or TrkC. We thus analyzed the physiological significance of NT-3 in ENS development. Subsets of neurons developing in vitro in response to NT-3 became NT-3 dependent; NT-3 withdrawal led to apoptosis, selectively in TrkC-expressing neurons. Antibodies to NT-3, which blocked the developmental response of enteric crest-derived cells to exogenous NT-3, did not inhibit neuronal development in cultures of isolated crest-derived cells but did so in mixed cultures of crest- and non-neural crest-derived cells; therefore, the endogenous NT-3 that supports enteric neuronal development is probably obtained from noncrest-derived mesenchymal cells. In mature animals, retrograde transport of (125)I-NT-3, injected into the mucosa, labeled neurons in ganglia of the submucosal but not myenteric plexus; injections of (125)I-NT-3 into myenteric ganglia, the tertiary plexus, and muscle, labeled neurons in underlying submucosal and distant myenteric ganglia. The labeling pattern suggests that NT-3-dependent submucosal neurons may be intrinsic primary afferent and/or secretomotor, whereas NT-3-dependent myenteric neurons innervate other myenteric ganglia and/or the longitudinal muscle. Myenteric neurons were increased in number and size in transgenic mice that overexpress NT-3 directed to myenteric ganglia by the promoter for dopamine beta-hydroxylase. The numbers of neurons were regionally reduced in both plexuses in mice lacking NT-3 or TrkC. A neuropoietic cytokine (CNTF) interacted with NT-3 in vitro, and if applied sequentially, compensated for NT-3 withdrawal. These observations indicate that NT-3 is required for the normal development of the ENS.
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10
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Abstract
Peptides involved in the endocrine and enteric nervous systems as well as in the central nervous system exert concerted action on gastrointestinal motility. Mechanical and chemical stimuli which induce peptide release from the epithelial endocrine cells are the earliest step in the initiation of peristaltic activities. Gut peptides exert hormonal effects, but peptide-containing stimulatory (Ach/substance P/tachykinin) and inhibitory (VIP/PACAP/NO) neurons are also involved in the induction of ascending contraction and descending relaxation, respectively. The dorsal vagal complex (DVC), located in the medulla of the brainstem, constitutes the basic neural circuitry of vago-vagal reflex control of gastrointestinal motility. Several gut peptides act on the DVC to modify vagal cholinergic reflexes directly (PYY and PP) or indirectly via afferent fibers in the periphery (CCK and GLP-1). The DVC is also a primary site of action of many neuropeptides (such as TRH and NPY) in mediating gastrointestinal motor activities. The identification over the last few years of a number of neuropeptide systems has greatly changed the field of feeding and body weight regulation. By exploring the brain and gut systems that employ recently identified peptidergic molecules, it will be possible to elaborate on the central and peripheral pathways involved in the regulation of gastrointestinal motility.
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Affiliation(s)
- M Fujimiya
- Department of Anatomy, Shiga University of Medical Science, Otsu, Shiga, Japan
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Ouyang A, Broussard DL, Feng HS. Action of substance P and interaction of calcitonin gene-related peptide and substance P on the cat antral circular muscle. REGULATORY PEPTIDES 1998; 77:25-32. [PMID: 9809793 DOI: 10.1016/s0167-0115(98)00033-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The actions of substance P (SP) and calcitonin gene-related peptide (CGRP) and their interaction were examined in vitro in the feline antrum and colon. Circular muscle contraction was seen in the antrum to both peptides, but only to SP in the proximal colon. Antral contraction was enhanced when both peptides were given together. This interaction was inhibited by tetrodotoxin or atropine. SP acted at the antrum via a smooth muscle neurokinin receptor which is not a (NK)-1 receptor. SP binding was displaced by neurokinin A but not by the NK-1 receptor antagonist, CP-96345. The colonic response was inhibited by CP-96345. Immunohistochemistry revealed SP-like immunoreactivity (SP-LI) in fibers in the antral myenteric plexus and circular muscle, while CGRP-like immunoreactivity (CGRP-LI) was seen in the myenteric plexus only, without co-localization. These studies supported the hypothesis that SP acted via the NK-2 receptor at the feline circular muscle in the antrum to induce contraction and at the NK-1 receptor in the proximal colon. CGRP enhanced the effect of SP via a cholinergic pathway.
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Affiliation(s)
- A Ouyang
- Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
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Timmermans JP, Adriaensen D, Cornelissen W, Scheuermann DW. Structural organization and neuropeptide distribution in the mammalian enteric nervous system, with special attention to those components involved in mucosal reflexes. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. PART A, PHYSIOLOGY 1997; 118:331-40. [PMID: 9366065 DOI: 10.1016/s0300-9629(96)00314-3] [Citation(s) in RCA: 87] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Gastrointestinal events such as peristalsis and secretion/absorption processes are influenced by the enteric nervous system, which is capable of acting largely independently from other parts of the nervous system. Several approaches have been used to further our understanding of the underlying mechanisms of specific enteric microcircuits. Apart from pharmacological and physiological studies, the deciphering of the chemical coding of distinct morphological and functional enteric neuron classes, together with a detailed analysis of their projections by the application of immunocytochemistry, of tracing, and of denervation techniques, have substantially contributed to our knowledge. In view of existing interspecies and regional differences, it is of major importance to expand our knowledge of the enteric nervous system in mammals other than the guinea-pig, the most commonly used experimental animal in this research area. This will increase our chances of finding a valid model, from which well-founded extrapolations can be made regarding the precise function of distinct enteric neuron types regulating motility and ion transport in the human gastrointestinal tract.
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Affiliation(s)
- J P Timmermans
- Laboratory of Cell Biology and Histology, University of Antwerp (RUCA), Belgium.
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14
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Teitelbaum DH, Del Valle J, Reyas B, Post L, Gupta A, Mosely RL, Merion R. Intestinal intraepithelial lymphocytes influence the production of somatostatin. Surgery 1996; 120:227-32; discussion 232-3. [PMID: 8751587 DOI: 10.1016/s0039-6060(96)80292-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND We have previously demonstrated that intestinal intraepithelial lymphocytes (iIELs) inhibit lymphocyte proliferation. Because somatostatin also prevents lymphocyte proliferation, we hypothesized that iIELs may influence production of somatostatin. METHODS Isolates of intestinal epithelium that were obtained from Brown Norway (BN) rats and contained an iIEL-enriched population (defined as CD45+) were incubated with irradiated Lewis splenocytes for allogeneic stimulation. BN rat splenocytes incubated with irradiated Lewis splenocytes served as a control. Supernatants were harvested after 4 days and assayed for somatostatin by using a radioimmunoassay. RESULTS The somatostatin level in the intestinal epithelium-conditioned supernatant was significantly higher than that of the control group (176 +/- 60 versus 10 +/- 2 fmol/ml; p < 0.05). Removal of the CD45+ cell subset resulted in a fifteenfold reduction in somatostatin levels. The CD45+ cell lysates had significantly higher levels of somatostatin than did CD45+ depleted cells (1304 +/- 531 versus 128 +/- 41 fmol/ml; p < 0.05). CONCLUSIONS The isolates of intestinal epithelium produced significant amounts of somatostatin. Removal of the CD45+ cells caused a significant loss of somatostatin production. Intracellular levels of somatostatin appeared to be highest in the CD45+ subpopulation. These data suggest that iIELs (that is, CD45+ cells) may have a significant influence on the production of somatostatin and may be a source of somatostatin production. Production of somatostatin by iIELs may help modulate immune responses in gut-associated lymphoid tissue.
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Affiliation(s)
- D H Teitelbaum
- Department of Surgery, University of Michigan Medical Center, Ann Arbor, USA
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15
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Furness JB, Young HM, Pompolo S, Bornstein JC, Kunze WA, McConalogue K. Plurichemical transmission and chemical coding of neurons in the digestive tract. Gastroenterology 1995; 108:554-63. [PMID: 7835599 DOI: 10.1016/0016-5085(95)90086-1] [Citation(s) in RCA: 126] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The enteric nervous system contains neurons with well-defined functions. However, when neurons of the same function are examined in different regions or species, they are found to show subtle differences in their pharmacologies of transmission and different chemical coding. Individual enteric neurons use more than one transmitter, i.e., transmission is plurichemical. For example, enteric inhibitory neurons have three or more primary transmitters, including nitric oxide, vasoactive intestinal peptide, and possibly adenosine triphosphate and pituitary adenylyl cyclase activating peptide. Primary transmitters are highly conserved, although their relative roles vary considerably between gut regions. Multiple substances, including transmitters and their synthesizing enzymes and nontransmitters (such as neurofilament proteins), provide neurons with a chemical coding through which their functions and projections can be identified. Although equivalent neurons in different regions have the same primary transmitters, other chemical markers differ substantially. Caution must be taken in extrapolating pharmacological and neurochemical observations between species or even between regions in the one species. On the other hand, careful interregion and interspecies comparisons lead to an understanding of the features of enteric neurons that are highly conserved and can be used in valid extrapolation.
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Affiliation(s)
- J B Furness
- Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Australia
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16
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Wardell CF, Bornstein JC, Furness JB. Projections of 5-hydroxytryptamine-immunoreactive neurons in guinea-pig distal colon. Cell Tissue Res 1994; 278:379-87. [PMID: 8001089 DOI: 10.1007/bf00414180] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The presence of 5-hydroxytryptamine in enteric neurons of the guinea-pig distal colon was demonstrated by immunohistochemistry and the projections of the neurons were determined. 5-Hydroxytryptamine-containing nerve cells were observed in the myenteric plexus but no reactive nerve cells were found in submucous ganglia. Varicose reactive nerve fibres were numerous in the ganglia of both the myenteric and submucous plexuses, but were infrequent in the longitudinal muscle, circular muscle, muscularis mucosae and mucosa. Reactivity also occurred in enterochromaffin cells. Lesion studies showed that the axons of myenteric neurons projected anally to provide innervation to the circular muscle and submucosa and to other more anally located myenteric ganglia. The results suggest that a major population of 5-hydroxytryptamine neurons in the colon is descending interneurons, most of which extend for 10 to 15 mm in the myenteric plexus and innervate both 5-hydroxytryptamine and non-5-hydroxytryptamine neurons.
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Affiliation(s)
- C F Wardell
- Department of Physiology, University of Melbourne, Parkville, Victoria, Australia
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Dhatt N, Buchan AM. Colocalization of neuropeptides with calbindin D28k and NADPH diaphorase in the enteric nerve plexuses of normal human ileum. Gastroenterology 1994; 107:680-90. [PMID: 7521306 DOI: 10.1016/0016-5085(94)90115-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND/AIMS The chemical coding of enteric neurons differs significantly among species. In the present study, the innervation of normal human ileum was characterized with respect to its chemical coding. METHODS The submucosa was subdivided into zones 1-3 based on its thickness and distribution of ganglia. The neuropeptides, calbindin D28k, and protein gene product 9.5 were identified by immunocytochemistry. Nitric oxide production was identified by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry. RESULTS Protein gene product 9.5 staining indicated that cell bodies of the submucosa could be subdivided into zones 1-3. Two major groups of submucosal cell bodies contained either substance P/somatostatin/calcitonin gene-related peptide or vasoactive intestinal peptide/neuropeptide Y/calbindin D28k. Gastrin-releasing peptide-containing cell bodies also colocalized with a subgroup of somatostatin cell bodies. No galanin, met-enkephalin, or NADPH diaphorase-positive cell bodies were present. In the myenteric plexus, the two major groups of cell bodies contained either calbindin or NADPH diaphorase. A proportion of the latter group costained with vasoactive intestinal peptide and met-enkephalin. Cell bodies containing substance P, somatostatin, and calcitonin gene-related peptide were present, forming three different subgroups. CONCLUSIONS Of the species investigated to date, the chemical coding of human ileal cell bodies most closely resembles that of the rat.
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Affiliation(s)
- N Dhatt
- Department of Physiology, University of British Columbia, Vancouver, Canada
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Houghton PE, Buchan AM, Challis JR. Ontogeny of the distribution and colocalization of Calbindin D28K within neural and endocrine cells of the gastrointestinal tract of fetal and neonatal sheep. ACTA ACUST UNITED AC 1992; 37:73-83. [PMID: 1347179 DOI: 10.1016/0167-0115(92)90656-f] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Using immunocytochemical techniques we have demonstrated that Calbindin D28K (CaBP) is present in the gastrointestinal tract of ovine fetuses early in development (by day 45). At day 45, CaBP was limited to neuronal elements in the developing intestine. By day 100, CaBP immunoreactivity was abundant in both epithelial endocrine cells and nerves of the submucous and myenteric ganglia. The location of CaBP containing cells and fibers was similar in duodenal sections taken from day 100 and term (145 days), as well as those taken from 24-48 h postnatal lambs. CaBP is colocalized in endocrine cells containing gastrin, glucagon, somatostatin and neurotensin, but not glucose dependent insulinotrophic peptide (GIP). Furthermore, it is extensively colocalized in nerve fibers and cells containing neurotensin but not somatostatin or vasoactive intestinal peptide. The colocalization of CaBP within various endocrine and nerve cells does not change in fetal sheep over the last one-third of gestation and there is no difference between fetal and neonatal sheep.
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Affiliation(s)
- P E Houghton
- Department of Obstetrics and Gynecology, University of Western Ontario, London, Canada
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Buchan AM, Kwok YN, Pederson RA. Anatomical relationship between neuropeptide-containing fibers and efferent vagal neurons projecting to the rat corpus. REGULATORY PEPTIDES 1991; 34:1-12. [PMID: 1713331 DOI: 10.1016/0167-0115(91)90219-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Injections of the retrograde tracers into the posterior surface of the stomach at the greater curvature resulted in labelling of the right half of the dorsal motor nucleus of the vagus. Whereas injections into the anterior and posterior surfaces of the corpus resulted in bilateral labelling in the medulla. Immunocytochemical staining of the labelled sections using antisera to substance P was confined to a dense network of fibers within the dorsal motor nucleus of the vagus and the nucleus tractus solitarius with no cell bodies being detected. Calcitonin gene-related peptide-immunoreactivity was detected in nerve fibers in the nucleus tractus solitarius and cell bodies of the hypoglossal nucleus. Finally, neuropeptide Y-immunoreactivity was confined to nerve fibers within the vagal complex. Of the neurons labelled by the retrograde tracers injected into the corpus all were in close spatial contact with fibers containing substance P-immunoreactivity. A smaller number were associated with neuropeptide Y-containing fibers with a few adjacent to calcitonin gene-related peptide-immunoreactive fibers. These results indicate that substance P and neuropeptide Y may directly regulate efferent neurons controlling gastric motility and acid secretion. Calcitonin gene-related peptide, however, is unlikely to directly modulate the cell bodies of the neurons in the dorsal motor nucleus but may modulate the dendrites from these neurons in the nucleus tractus solitarius.
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Affiliation(s)
- A M Buchan
- Department of Physiology, University of British Columbia, Vancouver, Canada
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Buchan AM. Neurofilament M and calbindin D28k are present in mutually exclusive subpopulations of enteric neurons in the rat submucous plexus. Brain Res 1991; 538:171-5. [PMID: 1708305 DOI: 10.1016/0006-8993(91)90394-b] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Immunocytochemical methods have been used to examine the localisation of 3 neurofilament proteins and the calcium binding protein, calbindin D28k, in whole mount preparations of the submucous plexus in the Wistar rat. Neurofilament-M (160 kDA protein) was present in 40% of the submucosal neurons, staining fine filaments in the soma and the axonal processes. Calbindin D28k was present in 40% of the submucosal neurons staining both the soma and nerves within the plexus. The neurofilament proteins and calbindin D28k were never observed within the same neurons. Neurofilament-M was co-localised with substance P and calcitonin gene-related peptide but not somatostatin or the other neuropeptides investigated. Calbindin D28k was co-localised with vasoactive intestinal polypeptide and neuropeptide Y. Galanin- and somatostatin-immunoreactive neurons did not contain either the neurofilament proteins or calbindin D28k. The results demonstrate the presence of subsets of submucosal neurons that can be distinguished by the presence of neurofilament-M or calbindin D28k.
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Affiliation(s)
- A M Buchan
- Department of Physiology, University of British Columbia, Vancouver, Canada
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