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Muscarinic M2 selective antagonism prolongs 5′‐AMP‐induced hypometabolism
Author(s) -
Strahota Mary Caitlin,
D’Alecy Louis George,
Zwemer Charles Frederick
Publication year - 2008
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.22.1_supplement.757.28
Subject(s) - muscarinic acetylcholine receptor , atropine , blockade , pirenzepine , chemistry , tonic (physiology) , methoctramine , endocrinology , medicine , pharmacology , receptor
Recent studies have shown that exogenous 5′‐adenosine monophosphate (5′‐AMP) induces a dose‐dependent hypometabolic state (HMS) in mice. Using indirect calorimetry, implantable telemetric probes, 5′‐AMP (913mg/Kg, i.p.), broad‐spectrum (atropine sulfate, 2mg/Kg i.p.), and subtype muscarinic antagonists (pirenzepine (M1), 0.2mg/Kg i.p. and methoctramine (M2), 0.2 mg/Kg i.p.), we tested the hypothesis that much of this effect in mice (C57BL6) was mediated by the parasympathetic nervous system. Atropine prolonged the HMS by 2.7 fold. Selective blockade of M2 similarly extended HMS while M1 blockade did not. Respiratory exchange ratio (RER) was elevated dramatically (≥ 1.5) during the HMS with atropine, but was lower (p=0.054) with M2 blockade suggesting a more adaptive steady state. These preliminary data suggest the 5′‐AMP‐induced HMS may be sustained by the withdrawal, inactivation, or blockade of tonic M2 effector mechanisms.