+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



Journal of Pharmacology and Experimental Therapeutics 278(2): 482-489



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)F1 alpha] 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-PGF1 alpha 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-PGF1 alpha 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-PGF1 alpha synthesis. 8-(4-chlorophenylthio) (cpt)-cAMP (10(-7) M) also inhibited ISOP-induced 6-keto-PGF1 alpha production. On the other hand, miconazole (10(-4) M), an inhibitor of adenylyl cyclase, reduced cAMP accumulation and enhanced ISOP-induced 6-keto-PGF1 alpha 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-PGF1 alpha synthesis produced by 10(-7) M ISOP and the inhibitory effect of cpt-cAMP and forskolin on 6-keto-PGF1 alpha production. 3-Isobutyl-1-methylxanthine, forskolin and cpt-cAMP did not alter the conversion of exogenous arachidonic acid to 6-keto-PGF1 alpha. 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.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 009034799

Download citation: RISBibTeXText

PMID: 8768695


Related references

Modulation by adenosine-35-cyclic monophosphate of beta adrenergic receptor -stimulated prostacyclin synthesis in rabbit ventricular myocytes. FASEB Journal 7(3-4): A472, 1993

Beta adrenergic receptor stimulated prostacyclin synthesis modulated by adenosine 35-cyclic monophosphate in rabbit coronary endothelial cells. FASEB Journal 8(4-5): A356, 1994

Beta adrenergic receptor stimulated prostacyclin synthesis in rabbit coronary endothelial cells is mediated by selective activation of phospholipase D: inhibition by adenosine 3'5'-cyclic monophosphate. Journal of Pharmacology and Experimental Therapeutics 281(3): 1038-1046, 1997

beta-Adrenergic modulation of prepulse facilitation of L-type calcium channels in rabbit ventricular myocytes. Pflugers Archiv 444(1-2): 89-98, 2002

Beta-2-Adrenergic receptor modulation of the action potential in rat ventricular myocytes. Biophysical Journal 70(2 PART 2): A392, 1996

Beta adrenergic receptor subtype modulation of calcium in ventricular myocytes. Biophysical Journal 68(2 PART 2): A181, 1995

Gi protein protects adult rat ventricular myocytes from beta-adrenergic receptor-stimulated apoptosis in vivo. Circulation 98(17 SUPPL ): I742, Oct 27, 1998

Matrix metalloproteinases mediate beta-adrenergic receptor-stimulated apoptosis in adult rat ventricular myocytes. American Journal of Physiology. Cell Physiology 289(1): C168-C176, 2005

Integrin signaling protects adult rat ventricular myocytes from beta-adrenergic receptor-stimulated apoptosis via activation of ERK1/2. Circulation 104(17 Supplement): II 142, October 23, 2001

Statins inhibit beta-adrenergic receptor-stimulated apoptosis in adult rat ventricular myocytes via a Rac1-dependent mechanism. Circulation 110(4): 412-418, 2004

beta1 integrins expression in adult rat ventricular myocytes and its role in the regulation of beta-adrenergic receptor-stimulated apoptosis. Journal of Cellular Biochemistry 89(2): 381-388, 2003

Beta1-adrenergic receptor stimulation inhibits alpha1-AR-stimulated hypertrophic signaling in adult rat ventricular myocytes via activation of cyclic AMP-protein kinase A cascade. Circulation 106(19 Supplement): II-48, November 5, 2002

Activation of mitogen-activated protein kinases protect against beta-adrenergic receptor-stimulated apoptosis in adult rat ventricular myocytes. Circulation 100(18 SUPPL ): I 64, Nov 2, 1999

Beta-adrenergic receptor-stimulated apoptosis in adult rat ventricular myocytes is mediated by a statin-sensitive Rac1-dependent mechanism. Circulation 108(17 Supplement): IV-116, October 28, 2003

Alpha 1-adrenergic activation inhibits beta-adrenergic-stimulated unitary Ca2+ currents in cardiac ventricular myocytes. Circulation Research 79(2): 184-193, 1996