TISSUE CONCENTRATIONS OF GASTROINTESTINAL REGULATORY PEPTIDES IN THE DUODENAL MUCOSA IN SYSTEMIC-SCLEROSIS

Objective: Esophageal hypomotility and abnormalities of intestinal fun ction are important manifestations in systemic sclerosis (SSc), but th eir pathogenesis is not well understood. Since there is evidence that plasma concentrations of certain gastrointestinal regulatory peptides are increased in SSc, we were interested in examining the peptide conc entrations and localization in biopsy specimens from the intestinal mu cosa in SSc patients. We identified 12 patients with gastrointestinal disease. Methods: Levels of corticotrophin-releasing hormone (CRH), mo tilin, neuropeptide Y (NPY) and peptide YY (PYY) were determined by ra dioimmunoassay and high-performance liquid chromatography (HPLC), and the occurrence of motilin, PYY, somatostatin, and NPY were studied wit h immunohistochemistry. Results: Except for the concentrations of CRH, which were increased 2-fold, the tissue concentration of motilin, NPY and PYY were decreased by approximately 50% among patients with esoph ageal and intestinal dysfunction (group B) compared to patients with i mpaired esophageal motility alone (group A). In addition, HPLC-charact erization of motilin, NPY, and PYY showed a different pattern of fragm ents among patients in groups A and B. In all patients duodenal motili n, PYY, and somatostatin were localized in the endocrine cells. The di stribution and frequency of the cells did not differ among the patient s. NPY was localized to neuronal elements; there was no overt differen ce among the patients with respect to the frequency of NPY-containing nerves. Conclusion: This study shows that patients with widespread gas trointestinal disease have lower tissue concentrations of regulatory p eptides compared to patients with less widespread disease.