Prejunctional muscarine receptors in the rabbit ear artery differ from M1, M2 and M3 muscarine receptors.
The ability of several selective muscarine receptor antagonists to inhibit the effect of carbachol on prejunctional muscarine receptors on sympathetic nerve endings in the rabbit isolated ear artery was investigated to characterise the receptor subtype involved. Carbachol did not reduce responses to exogenous noradrenaline and the inhibitory effect of carbachol on responses to nerve stimulation was unaffected by hexamethonium (10 microM) indicating that the effect of the muscarine agonist was exerted prejunctionally and was not modulated by nicotine receptor stimulation. The dissociation constants or apparent dissociation constants obtained using (+/-)-benzhexol (pKB; 6.63), (R)-benzhexol methiodide (8.11), dicyclomine (5.86), (+/-)-telenzepine (7.34), AF-DX 116 (6.95), himbacine (7.60), (+/-)-hexahydrosiladiphenidol (5.39) and a bisquaternary ammonium compound, heptane-1,7-bis(dimethyl-3'-phthalimidopropyl ammonium bromide) (5.84), indicate that the muscarine receptor subtype involved is not of the M1, M2 or M3 subtype.
Darroch
S A
SA
School of Pharmacology, Victorian College of Pharmacy (Monash University), Parkville, Australia.
Choo
L K
LK
Mitchelson
F
F
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000294:innervation / Q000648:ultrastructure*; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004025:Dicyclomine / Q000494:pharmacology; D004431:Ear, External / Q000098:blood supply*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000648:ultrastructure; D066298:In Vitro Techniques; D007700:Kinetics; D018727:Muscarinic Antagonists; D009130:Muscle, Smooth / Q000187:drug effects / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000187:drug effects / Q000648:ultrastructure; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000145:classification*; D014282:Trihexyphenidyl / Q000494:pharmacology
D006584:Hexamethonium Compounds; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D018738:Hexamethonium; D004025:Dicyclomine; D014282:Trihexyphenidyl; D002217:Carbachol