Bombesin-induced bronchoconstriction in the guinea pig: mode of action.
Bombesin is a potent bronchoconstrictor in guinea pigs in vivo, but the mechanisms of its effect are not certain. In vivo increases in tracheal pressure induced by bombesin were measured as an index of airway caliber. Bombesin (0.3-10 micrograms/kg) produced a dose-related bronchoconstrictor response in vivo which was not inhibited by indomethacin (5 mg/kg), BW A4C (50 mg/kg, a lipoxygenase inhibitor), WEB 2086 (10 micrograms/kg, a platelet-activating factor antagonist) or mepyramine (10 mg/kg, a histamine H1-receptor antagonist). Capsaicin pretreatment (50 mg/kg), which depletes neuropeptides from sensory nerve endings, similarly failed to inhibit the action of bombesin. Propranolol (1 mg/kg) produced a small shift to the left and atropine (1 mg/kg) and the serotonin antagonist, methysergide (1 mg/kg), produced a small shift to the right in the bombesin dose-response curve. The bombesin receptor antagonist, BIM 26159 (50 micrograms/kg), transiently inhibited bombesin-induced bronchoconstriction. Isoproterenol (0.1-10 micrograms/kg) reversed the increase in tracheal pressure induced by bombesin, suggesting that contraction of airway smooth muscle was involved. Bombesin (10(-10)-3 x 10(-5) M) failed to produce contraction in trachea or main bronchi either denuded of epithelium or in tissues pretreated with phosphoramidon, captopril or indomethacin (all 10(-5) M) and was inactive in peripheral lung strip preparations. Thus, bombesin is a potent constrictor of guinea pig airways in vivo. The inability of bombesin to contract airway smooth muscle in vitro suggests that the bronchoconstrictor action of bombesin is largely due to the release of an unidentified spasmogenic substance.
Belvisi
M G
MG
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Stretton
C D
CD
Barnes
P J
PJ
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001839:Bombesin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D011738:Pyrilamine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D011738:Pyrilamine; D001839:Bombesin; D007213:Indomethacin