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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1994-10-18
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pubmed:abstractText |
Previously, we demonstrated that low concentrations of acetylcholine (< or = 10(-9) M) increased automaticity in neonatal but not in adult rat ventricular myocardium. In the present study, we used cultured neonatal rat ventricular myocytes grown alone or in the presence of dissociated sympathetic neurons as an experimental model to study the ontogeny of the muscarinic response. McN A343 (< or = 10(-9) M), an M1 selective agonist, increased spontaneous rate from 51 +/- 4 to 56 +/- 5 beats per minute (bpm), and this excitatory response was blocked by 10(-9) M pirenzepine, an M1 selective antagonist, but not by the M2 selective antagonist AFDX-116, nor by the alpha 1 adrenergic antagonist prazosin and the beta adrenergic antagonist propranolol (all 10(-7) M) In innervated myocytes, McN A343 also increased rate from 48 +/- 6 to 55 +/- 6 bpm. However, this effect was blocked by either 10(-9) M pirenzepine or 10(-7) M propranolol. After pretreatment with 10 ng/ml of pertussis toxin, the McN A343-induced excitatory response in non-innervated myocytes was absent, thus suggesting that this response involved a pertussis toxin-sensitive G protein dependent pathway. McN A343 failed to stimulate inositol phosphate or cAMP accumulation in non-innervated myocytes. These results demonstrate the following. (1) The muscarinic excitatory response is mediated via direct stimulation of a post-synaptic M1 receptor in non-innervated myocytes. (2) The excitatory response after innervation is related to the release of catecholamines, possibly through activation of muscarinic receptors located at the pre-synaptic sympathetic nerve terminals. (3) Sympathetic innervation prevents the functional expression of the post-synaptic myocardial M1 receptor. (4) The intracellular pathway for the post-synaptic M1 excitatory response involves a pertussis toxin-sensitive G protein, but does not depend on obvious changes in cAMP or phosphoinositide hydrolysis.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/(4-(m-Chlorophenylcarbamoyloxy)-2-bu...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Muscarinic Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-2828
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
779-87
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7522276-(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium...,
pubmed-meshheading:7522276-Animals,
pubmed-meshheading:7522276-Cells, Cultured,
pubmed-meshheading:7522276-Cyclic AMP,
pubmed-meshheading:7522276-Heart,
pubmed-meshheading:7522276-Heart Rate,
pubmed-meshheading:7522276-Inositol Phosphates,
pubmed-meshheading:7522276-Muscarinic Antagonists,
pubmed-meshheading:7522276-Myocardial Contraction,
pubmed-meshheading:7522276-Myocardium,
pubmed-meshheading:7522276-Rats,
pubmed-meshheading:7522276-Receptors, Muscarinic,
pubmed-meshheading:7522276-Second Messenger Systems,
pubmed-meshheading:7522276-Sympathetic Nervous System,
pubmed-meshheading:7522276-Ventricular Function
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pubmed:year |
1994
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pubmed:articleTitle |
An excitatory muscarinic response in neonatal rat ventricular myocytes and its modulation by sympathetic innervation.
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pubmed:affiliation |
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York 10032.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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