Effects of cicletanine on histamine-induced contractions of isolated rabbit mesenteric arteries.
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) X 10(-8) M and 3.6 (+/- 0.3) X 10(-8) M, respectively. Cicletanine (greater than 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.
Laboratoire de Pharmacodynamie Générale et de Pharmacologie, Université Catholique de Louvain, Brussels, Belgium.
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D004232:Diuretics / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D011725:Pyridines; D011817:Rabbits
D000889:Anti-Arrhythmia Agents; D002132:Calcium Radioisotopes; D004232:Diuretics; D011725:Pyridines; D002110:Caffeine; D006632:Histamine; C038068:cicletanine; D009543:Nifedipine; D002118:Calcium