EFFECTS OF CICLETANINE ON HISTAMINE-INDUCED CONTRACTIONS OF ISOLATED RABBIT MESENTERIC ARTERIES

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Abstract
The antagonism by cicletanine of contractile responses to histamine has been examined in vitro on ring preparations of rabbit mesenteric arteries. Cicletanine (10-8-10-6 M) caused a parallel rightward shift of histamine concentration response curve, with a pA2 value of 7.48 (slope = 0.89 .+-. 0.19, not significantly different from unity). Histamine-induced contractions were nifedipine-sensitive and associated with cicletanine-sensitive increased 45Ca uptake. Endothelium removal resulted in enhanced contractile responses to histamine, but did not significantly modify cicletanine-induced antagonism: KB (dissociation constant) values for cicletanine antagonism in the presence or absence of endothelium were: 3.7 (.+-. 0.1) .times. 10-8 M and 3.6 (.+-. 0.3) .times. 10-8 M, respectively. Cicletanine (> 10-4 M) also significantly attenuated 10 mM caffeine-induced contractions in rings exposed to Ca-free 100 mM K+ depolarizing medium. The results suggest that cicletanine-induced antagonisms of histamine H1 receptor-mediated contractions of rabbit mesenteric arteries is associated with interference with calcium entry as well as at high concentrations, release from intracellular stores.