Contractile effect of bombesin on guinea pig lung in vitro: involvement of gastrin-releasing peptide-preferring receptors.
Bombesin (Bn) and related agonists produce a potent contractile response in guinea pig peripheral airways in vitro, with the following relative potencies: bombesin > gastrin-releasing peptide (GRP) > neuromedin C >> neuromedin B. Specific GRP-preferring receptor antagonists, namely [D-Phe6]Bn-(6-13)methyl ester and [D-Phe6,Cpa14,psi 13-14]Bn(6-14)-NH2, inhibited bombesin-induced lung contraction with high potencies [negative logarithm of the molar concentration of antagonist that produces a twofold shift to the right in the agonist dose-response curve (pA2) of 7.1 and 7.2, respectively], whereas the less-specific antagonist [Leu14,psi 13-14]Bn has a lower one (pA2 of 5.6). In binding studies, the high affinities of GRP, [D-Phe6]Bn(6-13)methyl ester and [D-Phe6,Cpa14,psi 13-14]Bn(6-14)NH2 in contrast with the low affinity of neuromedin B agree with the hypothesis that GRP-preferring receptors are involved in bombesin-induced bronchoconstriction. Bombesin-induced bronchoconstriction is unaffected by atropine, hexamethonium, propranolol, triprolidine, methysergide, Ro 19-3704, and indomethacin or AA-861, suggesting that the Bn response does not occur via a mechanism involving the corresponding endogeneous agents or via the release of arachidonic acid metabolites. Moreover, the effect of Bn is insensitive to capsaicin pretreatment, excluding the involvement of endogeneous neuropeptides. Present results provide evidence that Bn-induced bronchoconstriction results from a direct effect of Bn on bronchial smooth muscle GRP-preferring receptors.
Laboratoire de Neuroimmunopharmacologie pulmonaire, Institut National de la Santé et de la Recherche Médicale CJF 91-05, Université Louis Pasteur-Strasbourg I, Illkirch, France.
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D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008024:Ligands; D008168:Lung / Q000187:drug effects*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*
D008024:Ligands; D010446:Peptide Fragments; D010455:Peptides; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; C079531:bombesin (6-14)-NH2, Phe(6)-Cpa(14)-psi(13-14)-; C071101:bombesin (6-13), Phe(6) methyl ester-; D001839:Bombesin