ROLE OF DIFFERENT BOMBESIN RECEPTOR SUBTYPES MEDIATING CONTRACTILE ACTIVITY IN CAT UPPER GASTROINTESTINAL-TRACT

Mammalian bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) are known to increase the motility of different seg ments in the gut. The present study was carried out to identify the bo mbesin receptor subtypes mediating the contractions induced by exogeno us bombesin-like peptides in muscle strips isolated from cat esophagus , fundus, and duodenum. Both GRP-10 and NMB evoked concentration-depen dent contractions in circular strips of esophagus and fundus and in lo ngitudinal strips of the duodenum. These contractions were tetrodotoxi n-and atropine-resistant. The potency of NMB in esophageal strips was 33 times higher than that of GRP-10. The NMB-preferring receptor antag onists D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2 (SSocta) and D-Nal-cycl o[Cys-Tyr-D-Trp-Orn-Val-Cys]-Nal-NH2 (BIM-23127) shifted the NMB and G RP concentration-response curves to the right, while the GRP-preferrin g receptor antagonist [D-Phe(6)]Bombesin(6-13)-methyl-ester (BME) did not affect the response to the peptides. Isolated muscle strips from t he cat fundus and duodenum showed a higher sensitivity to GRP-10 than to NMB. In both segments, BME shifted the GRP-10 and NMB concentration -response curves to the right, while SSocta had no effect. The antagon ism of BME was competitive on duodenal but not competitive on fundic m uscle. We conclude that the direct myogenic action of GRP-10 and NMB i n the esophagus is mediated mainly via NMB-preferring receptors, while GRP-preferring receptors are responsible for the contractile response s to bombesin-like peptides in feline fundus and duodenum. Our data su ggest that the GRP receptor population located on fundic muscle might be nonhomogeneous. (C) 1998 Elsevier Science Inc.