EFFECT OF PINAVERIUM AND OTHER CALCIUM-CHANNEL BLOCKERS ON CONTRACTION OF ISOLATED GASTRIC ANTRAL SMOOTH-MUSCLE CELLS CAUSED BY GASTROINTESTINAL HORMONES

Gastrointestinal hormones,gastrin, cholecystokinin (CCK), and motilin, are known to induce contraction of digestive smooth muscle cells from various species. In this paper, we studied the effect of calcium chan nel blockers, diltiazem, nicardipine, and pinaverium on the hormone-de pendent contraction of smooth muscle cells isolated from rabbit antrum . Gastrin, CCK-8, and motilin caused dose-dependent contraction with E C-50 values in the physiological range (10-100 pM). This contractile e ffect was dependent upon extracellular calcium for gastrin and CCK-8 b ut not for motilin. When used alone, calcium channel blockers diltiaze m, nicardipine, but not pinaverium, caused a weak but significant cont raction of the cells. Pinaverium inhibited both gastrin- and CCK-8-ind uced contractions with IC-50 values of 1 nM and it was much less poten t in the inhibition of motilin-induced contractions (IC-50 = 25 nM). T he effect of pinaverium was equivalent to that of diltiazem in the inh ibition of CCK-8- or gastrin-induced contractions. Both drugs were sli ghtly more potent than nicardipine (IC-50 = 10 nM versus 1 nM for pina verium and 5 nM for diltiazem). In contrast, diltiazem and pinaverium were less potent against motilin stimulation, diltiazem being 5 times more potent than pinaverium. In conclusion, it appears that since Ca2 antagonists pinaverium, diltiazem and nicardipine inhibited contracti on of smooth muscle cells stimulated by gastrointestinal hormones, ''L -type'' calcium channels of the plasma membrane might,also be regulate d through occupation of gastrin or CCK receptors.