Bay K 8644 and Acetylcholine: Different Interaction with Calcium Ions in the Rat Duodenal Muscle

Abstract

The contractile effect of the dihydropyridine analogue Bay K 8644, recently described as a Ca2+-agonist, has been evaluated in the rat isolated duodenal muscle in comparison with that of acetylcholine, Bay K 8644 (3 .times. 10-10-10-6 mol/l) increased the duodenal motility, whereas it behaved as an inhibitor when tested at high concentrations (> 10-6 mol/l). Bay K 8644 was more potent than acetylcholine (threshold concentration 3 .times. 10-10 vs. 10-8 mol/l) but less efficient. The contractile responses to Bay K 8644 and acetylcholine were reduced in calcium-free medium and abolished by addition of 1 mmol/l EGTA. In some K+-depolarized tissues, however, a contractile response to Bay K 8644 was still observed. The effects of Bay K 8644 and acetylcholine were antagonized by nifedipine and verapamil; however, a competitive antagonism was observed only for the interaction Bay K 8644 nifedipine (pA2 = 9.86). The contraction induced by Bay K8644 was noncompetitively antagonized by low concentrations of atropine (10-7 mol/l); Bay K 8644 (10-7 mol/l) did not modify the response to acetylcholine, while inhibiting it at higher concentration (10-5 mol/l); in addition, it was able to enhance the response to endogenous acetylcholine, released by field stimulation. The above results indicated that Bay K 8644 and cholinergic stimuli are strong activators of the duodenal motility in vitro. The interference of Bay K 8644 with the cholinergic system, observed in both unstimulated and electrically stimulated strips, suggested a novel site of action of this compound in the gastrointestinal muscle.