We studied the expression of PTH-related peptide (PTHrP) and its mRNA in rat gastric smooth muscle in relation to various gastric motility states. Male rats were divided into groups subjected to fasting, feeding ad libitum, cold restraint stress, pyloric ligation, and carbachol stimulation. Cold restraint stress induced abnormal contractions. Rhythmic and moderate contractions were produced by carbachol administration, and marked distension was induced by pyloric ligation. PTHrP mRNA expression was weak in the physiological fasting and feeding states, but was markedly increased by pyloric ligation and carbachol stimulation. PTHrP and its mRNA were localized to the proper muscle layer and muscularis mucosa, but not in the mucosa by immunohistochemistry and in situ hybridization. The gene expression of PTHrP receptor in the gastric tissue was confirmed by reverse transcription-polymerase chain reaction, but serum PTHrP levels did not increase in all groups. These findings suggest that PTHrP acts as an autocrine or paracrine factor in gastric smooth muscle that responds to muscle activity caused by distension and cholinergic stimulation. However, PTHrP gene expression was decreased by stress despite the presence of strong contractions, and the sufficient relaxation did not occur. PTHrP suppression by stress is caused by the increase in corticosterone, as pretreatment of metyrapone, an inhibitor of 11 beta-hydroxylation, enhanced PTHrP gene expression in association with serum corticosterone suppression. In conclusion, PTHrP might be an important gastrointestinal peptide that regulates gastric contractile activity and is influenced by the serum corticosterone level.