Neuronal and myogenic muscarinic effects of McN-A-343 on guinea pig longitudinal smooth muscle-myenteric plexus

Abstract

Among muscarinic agonists, the compound McN-A-343, originally proposed as selective stimulant of M1 cholinergic site, was subsequently questioned as a useful pharmacological tool in the classification of muscarinic receptors. In this work, evidence is presented for a dual response of McN-A-343 on longitudinal muscle-myenteric plexus preparation. On electrically-stimulated preparation, this agonist exhibited a pirenzepine-sensitive inhibition of the twitch contractions due to the involvement of neural M1-muscarinic receptor. On the other hand, a direct myogenic contractile action on the unstimulated tissue was observed using McN-A-343 in the same range of concentrations. This latter response, on the basis of the effects of muscarinic and non-muscarinic antagonists tested, seems to involve effectorial muscarinic sites with an unusual mechanism.