Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6 Pt 2
pubmed:dateCreated
1997-8-18
pubmed:abstractText
Neonatal rat ventricular myocytes express both beta 1-and beta 2-adrenergic receptors linked to enhanced intracellular adenosine 3',5'-cyclic monophosphate (cAMP) accumulation and the modulation of contractile function. This study tests the hypothesis that muscarinic agonists act via distinct mechanisms to interfere with beta 1-and beta 2-adrenergic receptor actions. The beta 2-selective agonist zinterol (10(-7) M) elicits approximately a fourfold increase in cAMP accumulation, which is mimicked, both in magnitude and kinetics, by 10(-9) M of the mixed beta 1-receptor agonist/beta 2-receptor agonist isoproterenol. At these concentrations, isoproterenol and zinterol elicit equivalent inotropic and lusitropic (i.e., enhanced relaxation) responses. Carbachol inhibits all three responses (cAMP, inotropic, and lusitropic) elicited by isoproterenol. In contrast, carbachol does not interfere with the effect of zinterol to augment cAMP accumulation or to induce a positive inotropic response. However, carbachol inhibits the lusitropic response to zinterol via an action at an M2-muscarinic receptor linked to a pertussis toxin-sensitive pathway. Additional studies indicate that beta 2-receptor-dependent phosphorylation of troponin I and phospholamban is substantially attenuated by carbachol. We conclude that carbachol interferes with beta 1-receptor actions by reducing cAMP accumulation. In contrast, the anti-beta 2-receptor actions of carbachol are mediated by a mechanism that is distinct from inhibition of cAMP accumulation, involving an M2-muscarinic receptor coupled to a pertussis toxin-sensitive G protein, which leads to inhibition of troponin I and phospholamban phosphorylation and inhibition of the beta 2-receptor-dependent lusitropic response.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Carbachol, http://linkedlifedata.com/resource/pubmed/chemical/Cholinergic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP, http://linkedlifedata.com/resource/pubmed/chemical/Ethanolamines, http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta, http://linkedlifedata.com/resource/pubmed/chemical/Troponin I, http://linkedlifedata.com/resource/pubmed/chemical/phospholamban, http://linkedlifedata.com/resource/pubmed/chemical/zinterol
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H2726-35
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9227552-Adrenergic beta-Agonists, pubmed-meshheading:9227552-Adrenergic beta-Antagonists, pubmed-meshheading:9227552-Animals, pubmed-meshheading:9227552-Calcium-Binding Proteins, pubmed-meshheading:9227552-Carbachol, pubmed-meshheading:9227552-Cells, Cultured, pubmed-meshheading:9227552-Cholinergic Agents, pubmed-meshheading:9227552-Cyclic AMP, pubmed-meshheading:9227552-Drug Resistance, pubmed-meshheading:9227552-Ethanolamines, pubmed-meshheading:9227552-Heart Ventricles, pubmed-meshheading:9227552-Isoproterenol, pubmed-meshheading:9227552-Myocardial Contraction, pubmed-meshheading:9227552-Myocardium, pubmed-meshheading:9227552-Phosphorylation, pubmed-meshheading:9227552-Rats, pubmed-meshheading:9227552-Rats, Wistar, pubmed-meshheading:9227552-Receptors, Adrenergic, beta, pubmed-meshheading:9227552-Troponin I
pubmed:year
1997
pubmed:articleTitle
beta 1-and beta 2-adrenergic receptors exhibit differing susceptibility to muscarinic accentuated antagonism.
pubmed:affiliation
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't