Effects of the Calcium Antagonists Diltiazem, Verapamil and Nitrendipine on the Contractile Responses of Guinea-pig Isolated Ileum to Electrical Stimulation or Carbachol

Abstract

The effects of the organic Ca2+ antagonists nitrendipine, verapamil and diltiazem on the cholinergic contractile responses induced by field electrical stimulation or carbachol (0.1 microM) and on contractions evoked by high concentration KCl (30 mM) were studied in isolated preparations from the guinea-pig ileum. The three Ca2+ antagonists dose-dependently suppressed the contractile responses showing the same order of potency (nitrendipine greater than verapamil greater than diltiazem) with the three different types of stimulation. Comparison of the IC50 values of the Ca2+ antagonists for carbachol-, KCl- and electrically-evoked contractions demonstrated that the carbachol-evoked contractions were most sensitive to the inhibitory action of the antagonists tested. The presynaptic inhibitory effect of (Met)enkephalin (10 nM) on the electrically-evoked cholinergic contractions was only slightly potentiated by high concentrations (1 or 10 microM) of nitrendipine and diltiazem and remained unchanged by verapamil. The results suggest that the Ca2+ antagonists tested block mainly the carbachol-activated L-type Ca2+ channels on the smooth muscle cells, while the effects on the N-type Ca2+ channels are insignificant, except for the high concentrations of nitrendipine and diltiazem.

Presence of Antispasmodic, Antidiarrheal, Antisecretory, Calcium Antagonist and Acetylcholinesterase Inhibitory Steroidal Alkaloids inSarcococca saligna

“…However, verapamil did not show any such potentiating effect in spite of the fact it was shown to possess an AChE inhibitory effect in the in vitro assay. This was probably because verapamil is also known to possess an anticholinergic effect [11] which can mask such an effect as seen with the plant extract in the presence of atropine (Fig. 3).…”

Modification of Ca2+ Metabolism in the Rabbit Aorta as a Mechanism of Spasmolytic Action of Warifteine, a Bisbenzylisoquinoline Alkaloid Isolated from the Leaves of Cissampelos sympodialis Eichl. (Menispermaceae)

“…In the rabbit aorta, agonist-induced Ca2+ influx occurs without membrane depolarization (Droogmans et a1 1977;Van Breemen et a1 1985) and the influx through such receptor-operated channels is resistant to inhibitors of voltage-dependent Ca2+ channels (Bolton 1979;Stoytcheva & Venkova 1992). However, these receptor-operated channels are responsible for the sustained phase of the noradrenaline response and are blocked by agents such as nitroprusside which activates protein kinase G through cGMP generation (Karaki 1987;Moncada et a1 1987).…”

Antidiarrheal activity of Pyrenacantha staudtii Engl. (Iccacinaceae) aqueous leaf extract in rodents

“…It has been proposed by Reynolds et al (1984) that calcium antagonism is responsible, at least in part, for the antidiarrheal effect of loperamide and other compounds with calcium-antagonist properties like verapamil and diltiazem which exhibit spasmolytic properties on guinea pig ileum (Staneva-Stoytcheva and Venkova, 1992). Since Pyrenacantha staudtii, dose-dependently and significantly decreased normal intestinal propulsive movement and transit in rodents comparable to the standard antidiarrheal drug, loperamide, it is not unreasonable, therefore, to suggest that the calcium antagonist property of Pyrenacantha staudtii leaf aqueous extract may be due at least in part to its antidiarrheal effect observed in this study.…”