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PMID: 2825646 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Effects of forskolin on contractile responses and protein phosphorylation in the isolated perfused rat heart.

The Biochemical journal ·Vol. 246 ·No. 3 ·1987-09-15 ·Pages 687-95

England PJ, Shahid M

Abstract

Continuous perfusion of rat hearts with concentrations of forskolin between 0.1 and 12 microM resulted in transient increases in tension after 45 s, followed by a return to the control value after 5 min. In contrast, the content of cyclic AMP increased linearly with time over this period, reaching values up to 35 times control after 5 min. Increases in contractile force, intracellular cyclic AMP concentration and the proportion of phosphorylase in the a form were dependent on the concentration of forskolin when measured 45 s and 120 s after initiation of perfusion. In hearts perfused for 45 s with various concentrations of forskolin, the measured cyclic AMP-dependent protein kinase activity ratio and phosphorylase a content for a given measured intracellular cyclic AMP concentration were both much less than the corresponding values in hearts perfused for 30 s with various concentrations of isoprenaline. The phosphorylation of the contractile proteins troponin-I and C-protein also showed a concentration-dependent increase in hearts perfused with forskolin. There was a strong correlation between the cyclic AMP-dependent protein kinase activity ratios and the phosphorylation of the contractile proteins under all perfusion conditions. These results suggest that cyclic AMP is compartmented in perfused rat heart, and that much of the cyclic AMP produced in response to forskolin is unavailable to activate cyclic AMP-dependent protein kinase.

MeSH Terms
Animals Colforsin/pharmacology Cyclic AMP/metabolism Dose-Response Relationship, Drug Heart/drug effects In Vitro Techniques Muscle Proteins/metabolism Myocardial Contraction/drug effects Myocardium/metabolism Perfusion Phosphorylase a/metabolism Phosphorylation Protein Kinases/metabolism Rats Rats, Inbred Strains
Chemicals
Muscle Proteins Colforsin Cyclic AMP Phosphorylase a Protein Kinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
England P J
Department of Cellular Pharmacology, Smith, Kline & French Research Ltd., Welwyn, Herts, U.K.
Shahid M
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2460687
Published
1987-09-15
Pages
687-95
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1148333
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2460687 PMC Full Text View journal details
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