INHIBITORY MUSCARINIC CHOLINOCEPTORS ON POSTGANGLIONIC SYMPATHETIC-NERVES IN THE GUINEA-PIG ISOLATED ATRIUM ARE OF THE M(3) SUBTYPE

Pre- and postjunctional effects of four muscarinic (m)-cholinoceptor a ntagonists were investigated against carbachol in isolated spontaneous ly beating guinea pig atria which were also exposed to brief periods o f electrical field stimulation. The cholinoceptor agonist carbachol co ncentration-dependently inhibited the contraction rate of the atria wi th an EC(50) value of 92.3 +/- 20.6 nmol/l. The m-cholinoceptor antago nists atropine, 4-DAMP (M(1)- and M(3)-selective), AF-DX 116(M(2)-sele ctive) and pirenzepine (M(1)-selective) shifted the concentration-resp onse curves of carbachol to the right without modifying the maximal re sponses yielding pA(2) values of 8.98, 8.37, 7.44 and 6.79, respective ly. Electrical field stimulation increased the contraction rate of the atria which was potentiated by atropine or 4-DAMP while AF-DX 116 or pirenzepine had no significant effect. Therefore, on the basis of the findings with 4-DAMP, it is concluded that prejunctional m-cholinocept ors on the sympathetic nerve endings in guinea pig atria are inhibitor y and are of the M(3) subtype.