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 antagonists were investigated against carbachol in isolated spontaneously beating guinea pig atria which were also exposed to brief periods of electrical field stimulation. The cholinoceptor agonist carbachol concentration-dependently inhibited the contraction rate of the atria with an EC(50) value of 92.3 +/- 20.6 nmol/l. The m-cholinoceptor antagonists atropine, 4-DAMP (M(1)- and M(3)-selective), AF-DX 116(M(2)-selective) and pirenzepine (M(1)-selective) shifted the concentration-response curves of carbachol to the right without modifying the maximal responses yielding pA(2) values of 8.98, 8.37, 7.44 and 6.79, respectively. 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-cholinoceptors on the sympathetic nerve endings in guinea pig atria are inhibitory and are of the M(3) subtype.