Pleiotropic effects of bombesin and neurotensin on intestinal mucosa: Not just trefoil peptides

Abstract

Bombesin and neurotensin are neuropeptides which exert a wide spectrum of biological actions on gastrointestinal tissues influencing intestinal growth and adaptation, intestinal motility, blood flow, secretion, nutrient absorption and immune response. Based mainly on their well-established potent enterotrophic effect, numerous experimental studies investigated their potential positive effect on the atrophic or injured intestinal mucosa. These peptides proved to be effective mucosa-healing factors, but the potential molecular and cellular mechanisms for this action remained unresolved. In a recently published study (World J Gastroenterol 2008; 14(8): 1222-1230), it was shown that their protective effect on the intestine in experimentally induced inflammatory bowel disease was related to anti-inflammatory, antioxidant and antiapoptotic actions. These results are in close agreement with our previous studies on jaundiced and hepatectomized rats that showed a regulatory effect of bombesin and neurotensin on critical cellular processes such as enterocyte’ proliferation and death, oxidative stress and redox equilibrium, tight junctions’ formation and function, and inflammatory response. The pleiotropic effects of bombesin and neurotensin on diverse types of intestinal injury may justify their consideration for clinical trials.

Key Words: Bombesin, Neurotensin, Pleiotropic, Neuropeptides, Regulatory peptides

TO THE EDITOR

We read with great interest the recently published article (World J Gastroenterol 2008; 14(8): 1222-1230) by Dr. Akcan and colleagues[1], on the effect of neuropeptides Bombesin (BBS) and Neurotensin (NTS) on trinitrobenzene sulphonic acid-induced colitis in rats, an experimental model of colonic inflammatory bowel disease. In this nice set of experiments, the authors demonstrated the beneficial effects of both BBS and NTS on the preservation of intestinal macroscopic and microscopic integrity in experimental colitis. Most importantly, it was shown that this positive effect on the intestinal mucosa was related to anti-inflammatory, antioxidant and antiapoptotic actions.

It has been two decades since the issue of the potential beneficial role of BBS and NTS on preservation of intestinal homeostasis arose, based on peptides’ well-established potent enterotrophic effect[23]. Up to now, numerous experimental studies have demonstrated the protective effect of BBS and NTS against diverse types of intestinal injury, such as administration of elemental diets or methotrexate, induction of chemical colitis, burns, radiation therapy, ischemia/reperfusion and small bowel resection[3–9]. However, the molecular and cellular mechanisms implicated in their intestinal mucosa-healing effect remained unresolved for a long period. Our recent studies with jaundiced and hepatectomized rats showed that BBS and NT exert regulatory effects on critical cellular processes of enterocytes such as proliferation and death, oxidative stress, redox equilibrium, tight junctions’ formation and function, and inflammatory response[10–13]. The results presented in this study by Dr. Akcan et al are in close agreement with those previously reported by us and add further support to the hypothesis of a multifactorial mode of action of BBS and NT on the intestinal mucosa, beyond their trophic effect. The pleiotropic (mitogenic, antioxidant, antiapoptotic, anti-inflammatory and tight-junction modulating) effects of BBS and NT on intestinal mucosa and the wide range of intestinal injuries that could be healed or prevented by these peptides render BBS and NTS potential pivotal “gut-regulatory peptides” for many intestinal diseases. Although the authors very precisely state that the results of laboratory experiments are not readily applicable to the clinical situation, we feel that there is already a substantial experimental body of evidence supporting their consideration for clinical trials.