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 channel blockers, diltiazem, nicardipine, and pinaverium on the hormone-dependent contraction of smooth muscle cells isolated from rabbit antrum. Gastrin, CCK-8, and motilin caused dose-dependent contraction with EC-50 values in the physiological range (10-100 pM). This contractile effect was dependent upon extracellular calcium for gastrin and CCK-8 but not for motilin. When used alone, calcium channel blockers diltiazem, nicardipine, but not pinaverium, caused a weak but significant contraction of the cells. Pinaverium inhibited both gastrin- and CCK-8-induced contractions with IC-50 values of 1 nM and it was much less potent in the inhibition of motilin-induced contractions (IC-50 = 25 nM). The effect of pinaverium was equivalent to that of diltiazem in the inhibition of CCK-8- or gastrin-induced contractions. Both drugs were slightly more potent than nicardipine (IC-50 = 10 nM versus 1 nM for pineaverium 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 contraction of smooth muscle cells stimulated by gastrointestinal hormones, "L-type" calcium channels of the plasma membrane might also be regulated through occupation of gastrin or CCK receptors.

Anti-stomach serum induces contraction of isolated smooth muscle cells from gastric antrum.

In this work, we investigated the ability of anti-tissue sera to cause contraction of smooth muscle cells (SMC) in vitro. Therefore, we compared the effects of a horse immune serum raised against hog gastric tissue (SER 292), of its globulin fraction (SER 292 globulin), and of its IgG fraction (SER 292 IgG), on concentration of isolated SMC from the gastric antrum of the rabbit. Our results showed that SER 292 IgG induced a dose-dependent contraction of SMC with a higher potency than SER 292 globulin and SER 292. Preincubation of SER 292 globulin with anti-F(ab')2 but not with anti-Fc reduced the contractile activity of this anti-tissue serum. A serum raised against reticulo-endothelial system (SER 108) as well as a non immune serum (SENI) did not show any contractile activity. Our data provide evidence that SER 292 interacts with plasma membrane of SMC through its F(ab')2 fragments. Withdrawal of extracellular Ca2+ caused a significant reduction of the contractile effect induced by SER 292 IgG. When 45 Ca influx was measured, SER 292 IgG induced a specific and significant 45 Ca uptake which was blocked by pinaverium, a 'L-type' calcium channel blocker. These findings tend to show that contraction of SMC induced by SER 292 IgG involves an increase of intracellular Ca2+ concentration due in part to an influx of external Ca2+ via plasma membrane Ca2+ channels sensitive to 'L-type' channel blockers.