Inhibition of histamine-induced Ca2+ efflux in cultured vascular smooth muscle cells by an antihypertensive drug, cicletanine.
The effect of cicletanine, a new antihypertensive drug, on histamine-induced Ca2+ release in cultured vascular smooth muscle cells from guinea-pig aorta was examined. In 45Ca2+ labelled cells, histamine increased in a dose-dependent manner the Ca2+ efflux (EC50 = 8 x 10(-6) M). This stimulation of 45Ca2+ efflux was also observed with an H1-agonist [2-pyridylethylamine dihydrochloride (2-PEA)] but not with an H2-agonist (dimaprit). Histamine- or 2-PEA-induced 45Ca2+ efflux was inhibited by an H1-antagonist (mepyramine), whereas an H2-antagonist (cimetidine) had no effect. Cicletanine was as effective as the H1-antagonist in inhibiting histamine- or 2-PEA-stimulated 45Ca2+ efflux in a dose-dependent manner (IC50 = 10(-6) M). Only the racemic form and the R(-) enantiomer of cicletanine behaved as histaminergic antagonists, the S(+) enantiomer having no effect. These results suggest that the direct effect of cicletanine on the mobilization of Ca2+ by blocking H1-receptors may participate in an antihypertensive mechanism by producing relaxation of blood vessels.
Henri Beaufour Institute, Le Plessis-Robinson, France.
M O
MO
Lonchampt
J
J
Goulin
P E
PE
Chabrier
P
P
Braquet
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004232:Diuretics / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines
D000959:Antihypertensive Agents; D004232:Diuretics; D011725:Pyridines; D006632:Histamine; C038068:cicletanine; D002118:Calcium