INHIBITORY-ACTION OF MCN-A-343 ON ACETYLCHOLINE-INDUCED CONTRACTION IN MOLLUSCAN SMOOTH-MUSCLE

1. The effect of McN-A-343 (McN) on the contractile response to certain cholinergic agonists was investigated in the anterior byssus retractor muscle (ABRM) of Mytilus. 2. McN (3 x 10(-5) to 3 x 10(-4) M) dose-dependently inhibited the contractile response to acetylcholine (ACh), carbachol (CCh) and 1,1-dimethyl-4-phenyl-piperazinium (DMPP) in a noncompetitive manner. 3. McN (3 x 10(-5) to 3 x 10(-4)M) did not have any effect on the contractile response to KCl, caffeine or FMRF-NH2. 4. In the rectus abdominis muscle (RAM) of frog, McN produced a contractile response similar in potency to that produced by ACh, CCh and DMPP. 5. In the RAM, hexamethonium (C6) (3 x 10(-4)M) and d-tubocurarine (d-Tc) (3 x 10(-6)M) inhibited the contractile response to McN in a noncompetitive manner, and to CCh and DMPP in a competitive manner. 6. These findings indicate that McN, a selective M1 muscarinic agonist in mammalian tissues, acts as a nicotinic agonist in the PAM, and as a cholinergic antagonist in the ABRM.