Homologous desensitization of rat heart cells to beta-adrenergic stimulation and the absence of alpha-adrenergic or prostaglandin E1 effects

R A Fisher; I Harary; J A Thomas

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Journal article

Homologous desensitization of rat heart cells to beta-adrenergic stimulation and the absence of alpha-adrenergic or prostaglandin E1 effects

R A Fisher, I Harary and J A Thomas

Journal of cyclic nucleotide and protein phosphorylation research, Vol.9(6), pp.449-460

1983

PMID: 6151955

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Abstract

Epinephrine is shown to stimulate heart cell beating by both alpha- and beta-adrenergic mechanisms. The beta-adrenergic effect undergoes desensitization in one to two minutes after beta-agonist addition. A beta-antagonist did not cause desensitization. The desensitization response is quantitatively related to the concentration of cAMP produced in the cells. The alpha-adrenergic component of epinephrine action does not undergo desensitization nor does it have effects on the beta-adrenergic stimulation of cell beating or cAMP production. Other alpha-agonists and antagonists also have no effect on cAMP production. Prostaglandin E1 increased cellular cAMP by a mechanism that was additive with the beta-adrenergic mechanism. Both prostaglandin E1 and beta-agonists caused phosphorylation of both glycogen phosphorylase and glycogen synthase. Prostaglandin E1 did not desensitize the cells to beta-adrenergic stimulation of cAMP. The data show that heart cells undergo a rapid homologous desensitization to beta-agonists when treated with epinephrine or isoproterenol. The desensitization is quantitatively related to the cellular cAMP concentration, but cAMP produced by another mechanism does not desensitize the cells. No alpha-adrenergic effects on the beta-induced desensitization were observed.

Drug Resistance

Cells, Cultured

Prostaglandins E - pharmacology

Adrenergic beta-Agonists - pharmacology

Rats

Alprostadil

Heart Rate - drug effects

Animals

Myocardium - metabolism

Heart - drug effects

Adrenergic alpha-Agonists - pharmacology

Receptors, Adrenergic, beta - drug effects

Cyclic AMP - metabolism

Epinephrine - pharmacology

Details

Title: Subtitle: Homologous desensitization of rat heart cells to beta-adrenergic stimulation and the absence of alpha-adrenergic or prostaglandin E1 effects
Creators: R A Fisher
I Harary
J A Thomas
Resource Type: Journal article
Publication Details: Journal of cyclic nucleotide and protein phosphorylation research, Vol.9(6), pp.449-460
Publisher: United States
PMID: 6151955
ISSN: 0746-3898
Grant note: HL-13630 / NHLBI NIH HHS
Language: English
Date published: 1983
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040491602771

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