The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Prostaglandin $E_1$ Increases cGMP Levels in Beating Rabbit Atria: Lack of Effects of $PGE_1$-induced Cyclic Nucleotides on Secretory and Contractile Functions

  • Jin, Xuan Shun (Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School) ;
  • Quan, He Xiu (Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School) ;
  • Kim, Sun-Young (Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School) ;
  • Park, Sung-Hun (Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School) ;
  • Kim, Sung-Zoo (Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School) ;
  • Lee, Ho-Sub (Department of Herbal Resources, Wonkwang University Professional Graduate School of Oriental Medicine) ;
  • Cho, Kyung-Woo (Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School)
  • Published : 2007.10.31
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Abstract

Members of prostaglandin(PG) E-series elicit cellular effects mainly through adenylyl cyclase-cAMP signaling. The role of $PGE_2$-induced increase in cAMP has been shown to be compartmentalized in the cardiac myocytes: $PGE_2$-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 $PGE_1$ on the cGMP levels and the role of $PGE_1$ 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. $PGE_1$ increased cGMP as well as cAMP efflux concentration in a concentration-dependent manner, however, no significant changes in atrial secretory responses were observed(with $1.0{\mu}M\;PGE_1$; for cGMP, $144.76{\pm}37.5%$, n=11 versus $-16.81{\pm}4.76%$, n=6, control, p<0.01; for cAMP, $187.60{\pm}41.52%$, n=11 versus $7.38{\pm}19.44%$, n=6, control, p<0.01). $PGE_1$ decreased atrial dynamics slightly but transiently, whereas $PGE_2$ showed similar effects but with lower potency. Isoproterenol increased atrial cAMP efflux(with 2.0 nM; $145.71{\pm}41.89$, n=5 versus $7.38{\pm}19.44%$, n=6, control, p<0.05) and mechanical dynamics and decreased ANP secretion. The $PGE_1$-induced increase in cGMP efflux showed a bell-shaped concentration-response curve. $PGE_1$-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 $PGE_1$-induced transient decrease of atrial dynamics. These data indicate that $PGE_1$ increases cGMP levels via NO-soluble GC signaling in the cardiac atrium and also show that $PGE_1$-induced increases in cGMP and cAMP levels are not involved in the regulation of atrial secretory and contractile functions.

Keywords

References

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