Muscarinic receptor subtypes in equine tracheal smooth muscle.

Abstract

Selective muscarinic receptor antagonists were used to identify muscarinic receptor subtypes in equine trachealis strips. The M1 receptor antagonist pirenzepine (10(-7) mol/L to 3 x 10(-5) mol/L) and the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, 10(-9) mol/L to 3 x 10(-7) mol/L3) dose dependently inhibited the contractile responses to electrical field stimulation (EFS) and exogenous acetylcholine (ACh). Schild plots yielded a pA2 value for pirenzepine vs ACh of 6.75 +/- 0.09, which is consistent with the affinity for M2 or M3 receptors, and a pA2 value for 4-DAMP vs ACh of 8.47 +/- 0.09, which is in agreement with the affinity for M3 receptors. The M2 receptor antagonist gallamine (10(-5) mol/L and 10(-4) mol/L) did not affect the response of trachealis to exogenous ACh and low-frequency EFS (0.1-2 Hz) but decreased the responses to high-frequency EFS (4-16 Hz). These results suggest that the muscarinic receptors mediating contractions induced by ACh in equine tracheal smooth muscle are of the M3 subtype. The lack of an increase in the response to EFS following gallamine suggests that functional prejunctional inhibitory M2 receptors are not present on the cholinergic nerves innervating equine tracheal smooth muscle.