PREJUNCTIONAL MUSCARINIC AUTORECEPTORS ON HORSE AIRWAY CHOLINERGIC NERVES

Muscarinic autoreceptors on horse airway cholinergic nerves were studi ed by examining the effects of muscarinic receptor antagonists on elec trical field stimulation (EFS)-induced acetylcholine (ACh) release in trachealis preparations. All the antagonists including atropine (non-s elective), pirenzepine (M(1)-selective), AF-DX 116 (M(2)-selective), a nd hexahydrosiladifenidol (M(3)-selective) augmented ACh release conce ntration-dependently. The augmentation was not due to displacement of ACh molecules from tissue receptors into the bath liquid because incub ation with atropine after EFS had no influence on the measured amount of ACh. Hexahydrosiladifenidol was more potent in inhibiting ACh-induc ed muscle contraction, which is known to be mediated by M(3) receptors , than in augmenting ACh release. The maximal ACh release rate in resp onse to the selective antagonists was much less than that following at ropine. Furthermore, the concentrations of the selective antagonists r equired to augment ACh release far exceeded their K(d)s for M(1), M(2) , or M(3) receptors. These observations suggest that the muscarinic au toreceptors on horse airway cholinergic nerves may belong to a novel s ubtype.