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Characterization of prejunctional muscarinic autoreceptors in the guinea‐pig trachea
Author(s) -
Kilbinger H.,
Schneider R.,
Siefken H.,
Wolf D.,
D'Agostino G.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb09859.x
Subject(s) - methoctramine , muscarinic acetylcholine receptor , acetylcholine , autoreceptor , endocrinology , medicine , muscarinic acetylcholine receptor m3 , chemistry , muscarinic acetylcholine receptor m2 , biology , receptor , agonist
1 The effects of ten muscarinic antagonists on electrically evoked [ 3 H]‐acetylcholine release and muscle contraction were compared in an epithelium‐free preparation of the guinea‐pig trachea that had been preincubated with [ 3 H]‐choline. 2 The M 3 ‐selective antagonists UH‐AH 37, 4‐diphenyl‐acetoxy‐ N ‐piperidine methobromide and para ‐fluorohexahydrosiladiphenidol were more potent in reducing the contractile response than in facilitating the evoked [ 3 H]‐acetylcholine release. Hexahydrosiladiphenidol did not discriminate between pre‐ and postjunctional effects. The rank order of the postjunctional potencies of the ten antagonists as well as the postjunctional pA 2 values obtained for hexahydrosiladiphenidol (7.95) and AQ‐RA 741 (7.08) identified the muscular receptor as an M 3 subtype. 3 The M 2 ‐selective antagonists methoctramine, AF‐DX 116 and AQ‐RA 741 were more potent in facilitating the evoked [ 3 H]‐acetylcholine release than in inhibiting the contractile response. The increase in release by low concentrations of methoctramine, AF‐DX 116 and AQ‐RA 741 was paralleled by an enhancement of the stimulation‐evoked contractions. 4 Comparison of the pre‐ and postjunctional potencies of the M 1 ‐, M 2 ‐ and M 3 ‐selective antagonists suggests that autoinhibition of acetylcholine release is mediated via an ‘M 2 ‐like’ receptor which differs from the cardiac type M 2 receptor in its relatively high affinity for hexahydrosiladiphenidol.