Contractile effect of bombesin on guinea pig lung in vitro: involvement of gastrin-releasing peptide-preferring receptors
Lach, E.; Haddad, E.B.; Gies, J.P.
American Journal of Physiology 264(1 Pt 1): L80-L86
1993
ISSN/ISBN: 0002-9513 PMID: 8381599 Document Number: 412141
Bombesin (Bn) and related agonists produce a potent contractile response in guinea pig peripheral airways in vitro, with the following relative potencies: bombesin gt gastrinreleasing peptide (GRP) gt neuromedin CC mchgt neuromedin B. Specific GRP-preferring receptor antagonists, namely (D-Phe-6)Bn-(6-13)methyl ester and (D-Phe-6,Cpa-14, PSI 13-14)Bn(6-14)-NH-2, inhibiting 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-responses curve (pA-2) of 7.1 and 7.2, respectively), whereas the less-specific antagonist (Leu-14,PSI-13-14)Bn has a lower one (pA-2 of 5.6). In binding studies, the high affinities of GRP, (D-Phe-6)Bn(6-13)methyl ester and (D-Phe-6,Cpa-14, PSI-13-14)Bn(6-14)NH-2 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 or endogeneous neuropeptides. Present results provide evidence that Bn-induced bronchoconstriction results from a direct effect of Bn on bronchial smooth muscle GRP-preferring receptors.