Document Detail

Isoproterenol-induced restoration of contraction in K+-depolarized hearts: relationship to cAMP.
MedLine Citation:
PMID:  6267948     Owner:  NLM     Status:  MEDLINE    
The action of isoproterenol on inotropic state, cAMP concentration, and phosphorylase b-to-a conversion was studied under conditions that are known to alter membrane properties in guinea pig papillary muscles. In accord with the results of other investigators, contractile events induced by electrical stimulation were abolished by tetrodotoxin (10 microM) or 22 mM K+ and were subsequently restored by the addition of isoproterenol (10 nM-100 microM). However, in the presence of 22 mM K+, but not tetrodotoxin, the dose-response and temporal relationships between isoproterenol and elevations in cAMP concentration were shifted to the right, whereas those for phosphorylase activation were shifted to the left. Thus the low concentrations (less than 10 nM) of isoproterenol that restored tension development did not produce a measurable increase in cAMP. Contractile responses induced by 10 nM isoproterenol were blocked by (--)-propranolol but not by (+)-propranolol or phentolamine. Methoxamine did not restore contractile events in 22 mM K+-treated muscles or induce changes in cAMP content or phosphorylase activation. These results show that conditions can be obtained (e.g., partial depolarization of cardiac cell membranes) in which beta-adrenergic receptor activation leads to restoration of inotropic state in guinea pig myocardium without an obligatory increase in tissue cAMP content. The restoration of contractile events and enhancement of phosphorylase response under these conditions suggest that beta-adrenergic receptor activation may lead to Ca2+-channel activation directly or by increasing a small pool of cAMP and thereby altering localized protein phosphorylation in the cell membrane.
W R Ingebretsen; W F Friedman; S E Mayer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  241     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1981 Aug 
Date Detail:
Created Date:  1981-10-14     Completed Date:  1981-10-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H187-93     Citation Subset:  IM    
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MeSH Terms
Cyclic AMP / analysis*
Dose-Response Relationship, Drug
Guinea Pigs
Isoproterenol / pharmacology*
Muscle Contraction / drug effects
Myocardial Contraction / drug effects*
Papillary Muscles / enzymology
Phosphorylases / metabolism
Potassium / pharmacology*
Receptors, Adrenergic, alpha / physiology
Receptors, Adrenergic, beta / physiology
Tetrodotoxin / pharmacology
Time Factors
Grant Support
Reg. No./Substance:
0/Receptors, Adrenergic, alpha; 0/Receptors, Adrenergic, beta; 4368-28-9/Tetrodotoxin; 60-92-4/Cyclic AMP; 7440-09-7/Potassium; 7683-59-2/Isoproterenol; EC 2.4.1.-/Phosphorylases

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