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.
Ebeigbe
A B
AB
Laboratoire de Pharmacodynamie Générale et de Pharmacologie, Université Catholique de Louvain, Brussels, Belgium.
Cabanie
M
M
Godfraind
T
T
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