Stimulatory and inhibitory histamine receptors in canine cystic duct.

1 The effects of histamine receptor stimulation were assessed on the resistance of the canine cystic duct in vivo and on the contractility of circular muscle preparations of canine cystic duct in vitro. 2 In anaesthetized dogs, the H1-receptor agonist, 2-pyridylethylamine (0.05 to 15 mumol, i.a.), elicited dose-dependent increases in cystic duct resistance, whereas the H2-receptor agonist, 4-methylhistamine (0.05 to 15 mumol, i.a.) decreased cystic duct resistance. These responses were antagonized by the H1-receptor antagonist, diphenhydramine, and the H2-receptor antagonist, cimetidine, respectively. 3 Histamine (0.1 to 3000 nmol, i.a.) also increased cystic duct resistance in vivo. In the presence of diphenhydramine, the stimulatory effect of histamine was antagonized and slight decreases in cystic duct resistance became apparent. Cimetidine or prazosin also antagonized the stimulatory effects of histamine. 4 Histamine (1 to 100 microM) or 2-pyridylethylamine (1 to 100 microM) contracted, whereas 4-methylhistamine (1 to 100 microM) relaxed, circular muscle preparations of cystic duct. These excitatory and inhibitory responses were antagonized by diphenhydramine and cimetidine, respectively. 5 These results indicate that the canine cystic duct possesses excitatory H1- and inhibitory H2-receptors. The predominant effect of histamine is an H1-receptor-mediated increase in cystic duct resistance. Histamine, which may be released in association with cholecystitis, may exert significant effects on the regulation of bile flow in and out of the gallbladder and may contribute to gallbladder stasis during biliary disease.