Clinical Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 7, 2006; 12(37): 6002-6007
Published online Oct 7, 2006. doi: 10.3748/wjg.v12.i37.6002
Reduced expression of Ca2+-regulating proteins in the upper gastrointestinal tract of patients with achalasia
Harald Fischer, Judith Fischer, Peter Boknik, Ulrich Gergs, Wilhelm Schmitz, Wolfram Domschke, Jan W Konturek, Joachim Neumann
Harald Fischer, Judith Fischer, Wolfram Domschke, Medizinische Klinik und Poliklinik B, Universitätsklinikum Münster, 48129 Münster, Germany
Peter Boknik, Wilhelm Schmitz, Institut für Pharmakologie und Toxikologie, Universitätsklinikum Münster, 48149 Münster, Germany
Ulrich Gergs, Joachim Neumann, Institut für Pharmakologie und Toxikologie, Martin-Luther-Universität Halle-Wittenberg, 06112 Halle (Saale), Germany
Jan W Konturek, Klinik für Innere Medizin/Gastroenterologie, Elbe Klinikum Stade, 21682 Stade, Germany
Supported by grants from the “Deutsche Forschungsgemeinschaft” (DFG) and the Interdisciplinary Center of Clinical Research (IZKF) Münster
Correspondence to: Joachim Neumann, Institut für Pharmakologie und Toxikologie, Martin-Luther-Universität Halle-Wittenberg, Magdeburger Str. 4, 06112 Halle (Saale), Germany.
Telephone: +49-345-5571686 Fax: +49-345-5571835
Received: February 17, 2006
Revised: March 2, 2006
Accepted: March 10, 2006
Published online: October 7, 2006

AIM: To compare expression of Ca2+-regulating proteins in upper gastrointestinal (GI) tract of achalasia patients and healthy volunteers and to elucidate their role in achalasia.

METHODS: Sarcoplasmic reticulum Ca2+ ATPase (SERCA) isoforms 2a and 2b, phospholamban (PLB), calsequestrin (CSQ), and calreticulin (CRT) were assessed by quantitative Western blotting in esophagus and heart of rats, rabbits, and humans. Furthermore, expression profiles of these proteins in biopsies of lower esophageal sphincter and esophagus from patients with achalasia and healthy volunteers were analyzed.

RESULTS: SERCA 2a protein expression was much higher in human heart (cardiac ventricle) compared to esophagus. However, SERCA 2b was expressed predominantly in the esophagus. The highest CRT expression was noted in the human esophagus, while PLB, although highly expressed in the heart, was below our detection limit in upper GI tissue. Compared to healthy controls, CSQ and CRT expression in lower esophageal sphincter and distal esophageal body were significantly reduced in patients with achalasia (P < 0.05).

CONCLUSION: PLB in the human esophagus might be of lesser importance for regulation of SERCA than in heart. Lower expression of Ca2+ storage proteins (CSQ and CRT) might contribute to increased lower esophageal sphincter pressure in achalasia, possibly by increasing free intracellular Ca2+.

Keywords: Esophageal and gastric motility, Esophagus, Calsequestrin, Calreticulin