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PMID: 183151 Published · ppublish English Journal Article

Possible role of cyclic AMP in the relaxation process of mammalian heart: effects of dibutyryl cyclic AMP and theophylline on potassium contractures in cat papillary muscles.

Naunyn-Schmiedeberg's archives of pharmacology ·Vol. 293 ·No. 2 ·1976-05-00 ·Pages 129-37

Meinertz T, Nawrath H, Scholz H

Abstract

The effect of dibutyryl cyclic AMP (DB-c-AMP; 3 X 10(-4)-3 X 10(-3) M) on electrically induced twitch and high potassium (142.4 mM KCl)-induced contracture tension was studied in papillary muscles from normal and reserpinized cats ([Ca]0 1.8 mM; 25 degrees C; pH 7.4). In both groups of preparations, the increase in twitch tension evoked by DB-c-AMP was accompanied by an abbreviation of the time to peak force and of relaxation time. In the same preparations, the high potassium contracture was markedly depressed by DB-c-AMP in a concentration-dependent manner. Similar results were obtained with the N6-monobutyryl derivative of cyclic AMP. The relaxing effects of the cyclic nucleotides on KCl contractures did not appear to be due to possible non-cyclic breakdown products: adenosine, 5'-AMP and sodium butyrate did not attenuate contracture tension at concentrations up to 3 X 10(-3) M. The same applies to ATP and non-cyclic N6-2'-0-3'-0-tributyryl-adenosine-monophosphate. Theophylline (10(-2) M) was found to prolong the relaxation time of the twitch and to enhance the high KCl contracture. It is concluded that cyclic AMP may be capable of modulating the relaxation process of mammalian heart and that not only the positive inotropic but also the relaxant effects of catecholamines on myocardium described before may be mediated by the cyclic AMP system. The relaxant effects of cyclic AMP derivatives on intact myocardial preparations are attributed to a stimulation by cyclic AMP of the calcium transport of the sarcoplasmic reticulum (SR) and are interpreted to be a corollary to the effects of cyclic AMP previously obtained on isolated SR preparations.

MeSH Terms
Animals Biological Transport, Active/drug effects Bucladesine/pharmacology Calcium/metabolism Cats Cyclic AMP/analogs & derivatives,metabolism,physiology Myocardial Contraction/drug effects Norepinephrine/metabolism Papillary Muscles/physiology Potassium/pharmacology Reserpine/pharmacology Sarcoplasmic Reticulum/metabolism Theophylline/pharmacology
Chemicals
Bucladesine Reserpine Theophylline Cyclic AMP Potassium Calcium Norepinephrine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Meinertz T
Nawrath H
Scholz H
References (47)
47 references, click to expand
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Article Info
Journal
Naunyn-Schmiedeberg's archives of pharmacology
Abbr.
Naunyn Schmiedebergs Arch Pharmacol
ISSN
0028-1298
DOI
10.1007/BF00499217
Published
1976-05-00
Pages
129-37
Language
English
Region
Germany
NLM ID
0326264
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00499217 View journal details
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