EXPRESSION OF PARATHYROID HORMONE-RELATED PEPTIDE IN RELATION TO PERTURBATIONS OF GASTRIC-MOTILITY IN THE RAT

We studied the expression of PTH-related peptide (PTHrP) and its mRNA in rat gastric smooth muscle in relation to various gastric motility s tates. Male rats were divided into groups subjected to fasting, feedin g ad libitum, cold restraint stress, pyloric ligation, and carbachol s timulation. Cold restraint stress induced abnormal contractions. Rhyth mic and moderate contractions were produced by carbachol administratio n, and marked distension was induced by pyloric ligation. PTHrP mRNA e xpression was weak in the physiological fasting and feeding states, bu t was markedly increased by pyloric ligation and carbachol stimulation . PTHrP and its mRNA were localized to the proper muscle layer and mus cularis mucosa, but not in the mucosa by immunohistochemistry and in s itu hybridization. The gene expression of PTHrP receptor in the gastri c tissue was confirmed by reverse transcription-polymerase chain react ion, but serum PTHrP levels did not increase in all groups. These find ings suggest that PTHrP acts as an autocrine or paracrine factor in ga stric smooth muscle that responds to muscle activity caused by distens ion and cholinergic stimulation. However, PTHrP gene expression was de creased by stress despite the presence of strong contractions, and the sufficient relaxation did not occur. PTHrP suppression by stress is c aused by the increase in corticosterone, as pretreatment of metyrapone , an inhibitor of 11beta-hydroxylation, enhanced PTHrP gene expression in association with serum corticosterone suppression. In conclusion, PTHrP might be an important gastrointestinal peptide that regulates ga stric contractile activity and is influenced by the serum corticostero ne level.