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PMID: 1664725 Published · ppublish English Editorial Research Support, Non-U.S. Gov't Review

Signal transduction by cGMP in heart.

Basic research in cardiology ·Vol. 86 ·No. 6 ·1991-00-00 ·Pages 503-14

Lohmann SM, Fischmeister R, Walter U

Abstract

Early studies in whole heart indicated that cGMP antagonized the positive inotropic effects of catecholamines and cAMP. However, the regulation of cGMP levels by a variety of agents was not always consistent with their effects on contractility. It is now clear that at least two major cell types in whole heart, cardiac myocytes and vascular smooth muscle cells, differ markedly in their mechanisms of cGMP regulation and response to cGMP. Furthermore, experiments on isolated cardiac myocytes indicate that the mechanism of cGMP action even in this single cell type can be multifaceted. Cyclic GMP inhibits the L-type calcium channel current (ICa), which is the major source of Ca++ entry into heart cells, and which plays a predominant role in the initiation and regulation of cardiac electrical and contractile activities. Patch-clamp measurements of ICa indicate that in isolated frog myocytes cGMP inhibits ICa by stimulation of cAMP phosphodiesterase (cGS-PDE), whereas in purified rat ventricular myocytes, cGMP predominantly inhibits ICa via a mechanism involving cGMP-dependent protein kinase (cGMP-PK). Under certain conditions, cGMP can also inhibit a cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) and thereby produce a stimulatory effect on ICa. Biochemical characterization of the endogenous PDEs and cGMP-PK in purified cardiac myocytes provided further evidence in support of these mechanisms of cGMP action on ICa.

MeSH Terms
Animals Calcium/physiology Cyclic GMP/physiology Heart/physiology Humans Myocardium/cytology,metabolism Protein Kinases/metabolism Signal Transduction
Chemicals
Protein Kinases Cyclic GMP Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lohmann S M
Fischmeister R
Walter U
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Article Info
Journal
Basic research in cardiology
Abbr.
Basic Res Cardiol
ISSN
0300-8428
DOI
10.1007/BF02190700
Published
1991-00-00
Pages
503-14
Language
English
Region
Germany
NLM ID
0360342
Subset
IM
External Links
PubMed source DOI: 10.1007/BF02190700 View journal details
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