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KMID : 0811720070110050175
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Korean Journal of Physiology & Pharmacology
2007 Volume.11 No. 5 p.175 ~ p.182
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Prostaglandin E1 Increases cGMP Levels in Beating Rabbit Atria: Lack of Effects of PGE1-induced Cyclic Nucleotides on Secretory and Contractile Functions
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Jin Xuan-Shun
Kim Sung-Zoo
Cho Kyung-Woo
Lee Ho-Sub
Quan He-Xiu
Park Sung-Hun
Kim Sun-Young
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Abstract
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Members of prostaglandin (PG) E-series elicit cellular effects mainly through adenylyl cyclase-cAMP signaling. The role of PGE2-induced increase in cAMP has been shown to be compartmentalized in the cardiac myocytes: PGE2-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 PGE1 on the cGMP levels and the role of PGE1 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. PGE1 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 PGE1; 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). PGE1 decreased atrial dynamics slightly but transiently, whereas PGE2 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 PGE1-induced increase in cGMP efflux showed a bell-shaped concentration-response curve. PGE1-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 PGE1-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 PGE1-induced increases in cGMP and cAMP levels are not involved in the regulation of atrial secretory and contractile functions.
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KEYWORD
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Atrial function, Atrial natriuretic peptide, cAMP, cGMP, Prostaglandin E1
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