THE STIMULATORY ACTION OF THE CALCIUM-CHANNEL AGONIST BAY K-8644 ON ISOLATED DUODENAL MUSCLE - ANTAGONISM BY NIFEDIPINE AND VERAPAMIL

The action of the novel dihydropyridine analogue Bay K 8644 has been evaluated on the rat isolated duodenal muscle. Bay K 8644 (0.3 nmol/l to 1 pmol/l) increased both the tone and the phasic movements of the duodenum; the maximum response was about 60% of that to acetylcholine. Nifedipine (30 nmol/l) induced a parallel shift of the concentration-response curve to this compound to the right, without depressing the maximum response; conversely, verapamil (30 nmol/l) caused an unsurmountable antagonism. Incubation of the strips in Ca2+-free medium reduced the contractile response to the calcium agonist. The spasmogenic effect of Bay K 8644 was inhibited by atropine (0.1 pmol/l) which caused a significant reduction in the maximum repsonse to the compound. The competitive interaction between Bay K 8644 and nifedipine is consistent with an action at the same dihydropyridine binding site in the calcium channel and suggests that these compounds could be selective probes for detecting the dihydropyridine receptor also in the intestinal smooth muscle. The sensitivity of the contractile effect of Bay K 8644 to atropine may indicate an action of this compound in the cholinergic system, probably mediated by a release of acetylcholine from the nerve terminal rather than due to a direct stimulatory action at muscarinic receptor in the smooth muscle.