Pharmacological analysis of receptors for bombesin-related peptides on guinea pig gallbladder smooth muscle.

The aim of this study was to characterize the receptor(s) for bombesin (BN) and its homologues (gastrin releasing peptide, GRP; neuromedin B, NMB; neuromedin C, NMC) in guinea pig gallbladder muscle strips. Dose-dependent contractions were induced by all peptides tested (potency: BN = GRP > NMC > NMB, but with similar efficacy: BN = GRP = NMC = NMB). The contractions were resistant to tetrodotoxin, atropine, phentolamine, and propranolol. BN tachyphylaxis (1 microM) abolished subsequent contractile responses to BN, GRP and NMC; and partially antagonized the response to NMB (66 +/- 7% inhibition). NMB tachyphylaxis (10 microM) markedly inhibited subsequent contractile responses to NMB (78 +/- 5%); and partially antagonized the contractile response to BN (36 +/- 4%), GRP (31 +/- 12%) and NMC (22 +/- 2%). At 1 microM, both [D-Phe6, Des-Met14]-BN(6-14) ethylamide and ICI 216, 140, two BN receptor antagonists, reduced the contractile actions of BN (82 +/- 4% and 59 +/-8% inhibition, respectively), GRP (75 +/- 11% and 45 +/- 5%), and NMC (73 +/- 9% and 51 +/- 6%) while having no marked effect on NMB contractions. Our pharmacological approaches (receptor tachyphylaxis and differential antagonism) provide support for two types of receptors for BN-like peptides on guinea pig gallbladder smooth muscle: a GRP-preferring receptor and a NMB-preferring receptor.