Pre- and postjumntional muscarinic receptor subtypes in dog airways

Itabashi Sigeru, Aikawa Takashi, Sekizawa Kiyohisa, Ohrui Takashi, Sasaki Hidetada, Takishima Tamotsu

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    5 Citations (Scopus)

    Abstract

    To examine muscarinic receptor subtypes involved in cholinergically mediated contractions of the airway, we studied the effects of the M1-selective antagonist, pirenzepine, the M2-selective antagonist, AF-DX 116, the M3-selective antagonist, 4-diphenyl-acetoxy-N-methylpiperidine (4-DAMP) methiodide, and the non-selective antagonist, atropine, on acetylcholine (ACh)- and electrically induced contractions in dog bronchi and bronchioles. The relative potencies of the antagonists based on IC50 values of each antagonist for contractions induced by the two concentrations of ACh that produced 50% of the maximum (ed50) and the maximum (EDmax) contractions and the pA2 values were atropine ≥ 4-DAMP methiodide > pirenzepine = AF-DX 116 in both the bronchi and bronchioles. The IC50 and pA2 values of each antagonist did not differ significantly between the bronchi and bronchioles. 4-DAMP methiodide significantly inhibited the contractile response to electrical field stimulation (EFS) at 5 Hz at concentrations that did not alter the contractile responses to exogenous ACh in both the bronchi and bronchioles, whereas pirenzepine, AF-DX 116 and atropine inhibited the EFS-induced contraction only at the concentrations that reduced the contraction induced by exogenous ACh. The present results suggest that the cholinergic contraction is mediated via the postsynaptic receptor M 3, based on functional potencies of muscarinic antagonists and presynaptic receptor auto-facilitatory M3, based on the suppression of the contractile response to EFS by 4-DAMP methiodide in central and peripheral airways.

    Original languageEnglish
    Pages (from-to)235-241
    Number of pages7
    JournalEuropean Journal of Pharmacology
    Volume204
    Issue number3
    DOIs
    Publication statusPublished - 1991 Nov 12

    Keywords

    • Acetylcholine release
    • Bronchioles
    • Muscarinic M receptors

    ASJC Scopus subject areas

    • Pharmacology

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