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. 1991 Jul;103(3):1757–1763. doi: 10.1111/j.1476-5381.1991.tb09859.x

Characterization of prejunctional muscarinic autoreceptors in the guinea-pig trachea.

H Kilbinger 1, R Schneider 1, H Siefken 1, D Wolf 1, G D'Agostino 1
PMCID: PMC1907820  PMID: 1933138

Abstract

1. The effects of ten muscarinic antagonists on electrically evoked [3H]-acetylcholine release and muscle contraction were compared in an epithelium-free preparation of the guinea-pig trachea that had been preincubated with [3H]-choline. 2. The M3-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 [3H]-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 pA2 values obtained for hexahydrosiladiphenidol (7.95) and AQ-RA (7.08) identified the muscular receptor as an M3 subtype. 3. The M2-selective antagonists methoctramine, AF-DX 116 and AQ-RA 741 were more potent in facilitating the evoked [3H]-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 M1-, M2- and M3-selective antagonists suggests that autoinhibition of acetylcholine release is mediated via an 'M2-like' receptor which differs from the cardiac type M2 receptor in its relatively high affinity for hexahydrosiladiphenidol.

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Selected References

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