AUTOREGULATION OF ACETYLCHOLINE-RELEASE FROM VAGUS NERVE-TERMINALS INTHE DOG TRACHEA

We examined the effects of M(1), M(2) and M(3) selective antagonists ( pirenzepine, AF-DX116 and 4-DAMP) and of the agonists McNeil A343 (M(1 )), pilocarpine (M(2)) and oxotremorine and bethanechol (M(2) and M(3) ) on the excitatory junctional potential (EJP) amplitude evoked by sin gle electrical field stimulation (EFS) in the dog trachea. Pirenzepine at relatively low concentrations enhanced and at high concentrations suppressed the EJP with no significant change in resting membrane pote ntial and input resistance of the smooth muscle cell. AF-DX116 or 4-DA MP, on the other hand, dose-dependently suppressed the EJP. McNeil A34 3, an M(1) agonist, suppressed the EJP in a dose-dependent manner. How ever, pilocarpine, an M(2) agonist, and oxotremorine and bethanechol, that are non-selective M(2) and M(3) agonists, showed biphasic action on the EJP. Thus, at relatively low concentrations these agents enhanc ed and at high concentrations suppressed the EJP. From these results, we conclude the subtype of prejunctional autoreceptor which inhibits t he ACh release in the dog trachea is not M(2) but M(1) subtype.