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Functional role of muscarinic M 2 receptors in α,β ‐methylene ATP induced, neurogenic contractions in guinea‐pig ileum
Author(s) -
Sawyer Gregory W,
Lambrecht Günter,
Ehlert Frederick J
Publication year - 2000
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 - 10.1038/sj.bjp.0703180
Subject(s) - muscarinic acetylcholine receptor , acetylcholine , histamine , chemistry , endocrinology , medicine , oxotremorine , muscarinic acetylcholine receptor m2 , carbachol , pertussis toxin , muscarinic acetylcholine receptor m3 , agonist , muscarinic agonist , muscarinic acetylcholine receptor m1 , pharmacology , receptor , biology , biochemistry , g protein
The muscarinic acetylcholine receptors mediating the contractile response elicited to endogenous acetylcholine released by the selective P2X receptor agonist α,β‐methylene ATP (mATP) were investigated in guinea‐pig ileum. mATP (0.1–30 μ M ) elicited a concentration‐dependent neurogenic contractile response inhibited by tetrodotoxin (TTX) and antagonized by the non‐selective muscarinic receptor antagonist N‐methylscopolamine (NMS). The contractile response to mATP was pertussis toxin‐insensitive, irreversibly antagonized by N‐(2‐chloroethyl)‐4‐piperidinyl diphenylacetate (4‐DAMP mustard), and unaffected by the muscarinic M 2 /M 4 receptor selective antagonist AF‐DX 116 (1 μ M ). When measured in the presence of histamine and isoproterenol after treatment with 4‐DAMP mustard, mATP elicited a pertussis toxin‐sensitive contractile response potently antagonized by AF‐DX 116. Collectively, our data suggest that endogenous acetylcholine released by mATP can elicit a direct contractile response through the muscarinic M 3 receptor and an indirect contractile response through the muscarinic M 2 receptor by antagonizing the relaxant effects of isoproterenol on histamine induced contraction.British Journal of Pharmacology (2000) 129 , 1458–1464; doi: 10.1038/sj.bjp.0703180