Prostaglandin E<SUB>1</SUB> Increases cGMP Levels in Beating Rabbit Atria: Lack of Effects of PGE<SUB>1</SUB>-induced Cyclic Nucleotides on Secretory and Contractile Functions

Prostaglandin E<SUB>1</SUB> Increases cGMP Levels in Beating Rabbit Atria: Lack of Effects of PGE<SUB>1</SUB>-induced Cyclic Nucleotides on Secretory and Contractile Functions

Members of prostaglandin (PG) E-series elicit cellular effects mainly through adenylyl cyclase-cAMP signaling. The role of PGE<SUB>2</SUB>-induced increase in cAMP has been shown to be compartmentalized in the cardiac myocytes: PGE<SUB>2</SUB>-induced increase of cAMP is not involved in the control of cardiomyocytic contraction. The purpose of the present study was to define the effect of PGE<SUB>1</SUB> on the cGMP levels and the role of PGE<SUB>1</SUB> in the atrial secretory function. Experiments were performed in perfused beating rabbit atria and atrial contractile responses, cGMP and cAMP efflux, and atrial natriuretic peptide (ANP) secretion were measured. PGE<SUB>1</SUB> increased cGMP as well as cAMP efflux concentration in a concentration-dependent manner, however, no significant changes in atrial secretory responses were observed (with 1.0μM PGE<SUB>1</SUB>; for cGMP, 144.76±37.5%, n=11 versus －16.81±4.76%, n=6, control, p＜ 0.01; for cAMP, 187.60±41.52%, n=11 versus 7.38±19.44%, n=6, control, p＜0.01). PGE<SUB>1</SUB> decreased atrial dynamics slightly but transiently, whereas PGE<SUB>2</SUB> showed similar effects but with lower potency. Isoproterenol increased atrial cAMP efflux (with 2.0 nM; 145.71±41.89, n=5 versus 7.38±19.44%, n=6, control, p＜0.05) and mechanical dynamics and decreased ANP secretion. The PGE<SUB>1</SUB>-induced increase in cGMP efflux showed a bell-shaped concentration-response curve. PGE<SUB>1</SUB>-induced increase of cGMP efflux was not observed in the presence of L-NAME, an inhibitor of nitric oxide (NO) synthase, or ODQ, an inhibitor of NO-sensitive guanylyl cyclase. L-NAME and ODQ showed no significant effect on the PGE<SUB>1</SUB>-induced transient decrease of atrial dynamics. These data indicate that PGE1 increases cGMP levels via NO-soluble GC signaling in the cardiac atrium and also show that PGE<SUB>1</SUB>-induced increases in cGMP and cAMP levels are not involved in the regulation of atrial secretory and contractile functions.