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Role of the M 2 muscarinic receptor in contraction of mouse urinary bladder
Author(s) -
Pak Kirk J,
Park Grace J,
Ahn Simon,
Sangnil Marline S,
Matsui Minoru,
Ostrom Rennolds S,
Ehlert Frederick J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1162
Subject(s) - muscarinic acetylcholine receptor , oxotremorine , endocrinology , agonist , medicine , chemistry , muscarinic acetylcholine receptor m3 , contraction (grammar) , muscarinic acetylcholine receptor m1 , stimulation , muscarinic agonist , acetylcholine , muscarinic acetylcholine receptor m2 , muscarinic acetylcholine receptor m4 , urinary bladder , receptor
We investigated whether activation of the M 2 muscarinic receptor inhibits the relaxant effect of isoproterenol on contraction elicited by other receptors. The muscarinic agonist oxotremorine‐M caused a weak contraction in urinary bladder from M 3 knockout (KO) mice. When measured in the same tissue in the presence of isoproterenol and α,β‐methylene‐ATP, oxotremorine‐M elicited a robust contractile response, but not in bladder from M 2 /M 3 double KO mice. Similar results were observed when PGF2α was used as the non‐muscarinic contractile agent, but not α‐methyl‐serotonin. The combination of isoproterenol and contractile agent (i.e. α,β‐methylene‐ATP, PGF2α or α‐methyl‐serotonin) had little effect because of their opposing actions on contraction. To address whether neuronally released acetylcholine acts on the M 2 receptor to inhibit relaxation by isoproterenol, we investigated electrical field stimulation of mouse urinary bladder (0.2 Hz, 2 msec duration, 100 V) in the presence of physostigmine (70 nM). Isoproterenol was approximately 12‐fold more potent at inhibiting field‐stimulated contractions of urinary bladder from M 2 KO mice compared to wild type. Our results show that neuronally released or exogenously applied muscarinic agonist can act on the M 2 muscarinic receptor to oppose ß‐adrenoceptor‐mediated relaxation of the detrusor. Supported by the MSTP grant and NIH grant HL079166.