Modulation by cyclic AMP of beta adrenergic receptor-stimulated prostacyclin synthesis in rabbit ventricular myocytes

Ying Ruan, Hong Kan, Kafait Malik

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The purpose of the present study was to determine the possible interaction of cyclic AMP (cAMP) and the synthesis of prostacyclin [measured as immunoreactive 6-keto-prostaglandin (PG)F(1α)] elicited by the beta adrenergic receptor agonist isoproterenol (ISOP), in freshly dissociated rabbit ventricular myocytes. ISOP (10-13 to 10-11 M) increased 6-keto- PGF(1α) synthesis without altering the level of cAMP. Increasing the concentration of ISOP from 10-10 to 10-7 M enhanced accumulation of cAMP, which was associated with a decline in 6-keto-PGF(1α) synthesis. Forskolin (10-6 M), an activator of adenylyl cyclase, and 3-isobutyl-1- methylxanthine (10-5 M), an inhibitor of cAMP phosphodiesterase, increased cAMP accumulation and inhibited ISOP-induced 6-keto-PGF(1α) synthesis. 8- (4-chlorophenylthio) (cpt)-cAMP (10-7 M) also inhibited ISOP-induced 6- keto-PGF(1α) production. On the other hand, miconazole (10-4 M), an inhibitor of adenylyl cyclase, reduced cAMP accumulation and enhanced ISOP- induced 6-keto-PGF(1α) synthesis in myocytes. Miconazole also attenuated ISOP-, forskolin- and cpt-cAMP-induced increases in protein kinase A activity. The protein kinase A inhibitor H-89 {N-[2-(p- bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide} attenuated the ISOP (10-7 M)-induced increase in the activity of this enzyme and minimized the decline in 6-keto-PGF(1α) synthesis produced by 10-7 M ISOP and the inhibitory effect of cpt-cAMP and forskolin on 6-keto-PGF(1α) production. 3- Isobutyl-1-methylxanthine, forskolin and cpt-cAMP did not alter the conversion of exogenous arachidonic acid to 6-keto-PGF(1α). These data indicate that beta adrenergic receptor activation promotes prostacyclin synthesis in rabbit ventricular myocytes and that cAMP acts as an inhibitory modulator. This action is mediated via activation of protein kinase A, probably by decreasing the activity of the lipase, involved in beta adrenergic receptor-induced arachidonic acid release.

Original languageEnglish (US)
Pages (from-to)482-489
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume278
Issue number2
StatePublished - Aug 1 1996
Externally publishedYes

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Receptors, Adrenergic, beta
Epoprostenol
Cyclic AMP
Muscle Cells
Prostaglandins F
Isoproterenol
Rabbits
Colforsin
Cyclic AMP-Dependent Protein Kinases
Miconazole
1-Methyl-3-isobutylxanthine
Arachidonic Acid
Adrenergic beta-1 Receptor Agonists
Phosphoric Diester Hydrolases
Protein Kinase Inhibitors
Lipase
Adenylyl Cyclases

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Modulation by cyclic AMP of beta adrenergic receptor-stimulated prostacyclin synthesis in rabbit ventricular myocytes. / Ruan, Ying; Kan, Hong; Malik, Kafait.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 278, No. 2, 01.08.1996, p. 482-489.

Research output: Contribution to journalArticle

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