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Regulation of the cAMP-elevating effects of isoproterenol and forskolin in cardiac myocytes by treatments that cause increases in cAMP.

Abstract：

:Regulation of the cAMP-elevating effects of isoproterenol and forskolin in cardiac myocytes by treatments that cause increases in cAMP. We have found that elevations in cyclic AMP (cAMP) have long-term effects on both the beta-adrenergic receptor and adenylyl cyclase in cultured chick ventricular myocytes. Pretreatment with isoproterenol for 15min markedly reduced the cAMP-elevating effect of a subsequent treatment with isoproterenol 18h later. Responses to isoproterenol were similarly reduced after overnight treatments with forskolin or phosphodiesterase inhibitors. Furthermore, these same treatments also markedly blunted the cAMP-elevating effect of forskolin, a direct activator of adenylyl cyclase. The blunting of the isoproterenol effect was greater than that of the forskolin effect, at least partially because the pretreatments caused a decrease in the number of beta-adrenergic receptors as well as a net decrease in adenylyl cyclase activity. Experiments with a recombinant adenovirus to express luciferase under the control of cAMP responsive elements (CREs) showed that the same treatments elevated cAMP sufficiently to drive the transcription of a gene with CREs in its promoter. The blunting of both the isoproterenol and forskolin responses was blocked by the inhibition of protein synthesis or by infecting cells with a recombinant adenovirus that expresses rabbit muscle cAMP-dependent protein kinase inhibitor (PKI). It is hypothesized that one or more adenylyl cyclase isozymes responsible for the generation of cAMP in the myocytes, along with other proteins previously reported to regulate beta-adrenergic receptors and perhaps adenylyl cyclase, are negatively regulated by cAMP, most likely at the level of gene expression, and that this regulation may have therapeutic consequences in the treatment of cardiac diseases.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Cui H,Green RD

doi

10.1016/s0006-291x(03)01130-6

subject

Has Abstract

pub_date

2003-07-18 00:00:00

pages

119-26

issue

eissn

0006-291X

issn

1090-2104

pii

S0006291X03011306

journal_volume

307

pub_type

杂志文章

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Regulation of the cAMP-elevating effects of isoproterenol and forskolin in cardiac myocytes by treatments that cause increases in cAMP.