Stimulation of placental prorenin secretion by selective inhibition of cyclic nucleotide phosphodiesterases

Biochemical Pharmacology
G J Downing, A M Poisner

Abstract

Prorenin secretion by human villous placenta is known to be stimulated by activation of adenylate cyclase and enhanced cyclic AMP (cAMP) generation. Placental tissue contains predominantly type III (cGMP-inhibited) and type IV (cAMP-specific) phosphodiesterases (PDEs), which inactivate cAMP. To evaluate the role of PDE subtypes in the regulation of prorenin secretion by human placenta, explants were cultured in the presence of isobutylmethylxanthine (IBMX), a non-selective PDE inhibitor, and selective inhibitors for various PDE subtypes. Inhibition of PDE subtypes with cilostamide (type III), Ro 20-1724 (type IV) and zardaverine (types III and IV) increased prorenin release. Inhibition of type I (Ca(2+)/calmodulin-dependent) PDE by 8-MeoM-IBMX and of type V (cGMP-specific) PDE by zaprinast or dipyridamole did not affect prorenin secretion. The stimulation of prorenin secretion by PDE inhibitors was attenuated by cAMP-dependent protein kinase inhibition. The selective PDE inhibitors caused a parallel increase in media cAMP and prorenin and also increased tissue prorenin levels. These studies demonstrate that cAMP degradation by type III and IV PDE isoenzymes is a major regulatory mechanism for placental prorenin secretion. It is...Continue Reading

References

Mar 26, 1991·European Journal of Pharmacology·F A Le NobleH A Struyker Boudier
Apr 1, 1990·Trends in Pharmacological Sciences·J A Beavo, D H Reifsnyder
Jan 1, 1985·Endocrinology·J J Moore, R C Cardaman
Aug 1, 1985·Prostaglandins, Leukotrienes, and Medicine·G A LopezS Rivas
Aug 1, 1993·Nihon Hinyōkika Gakkai zasshi. The japanese journal of urology·N Kondoh

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Citations

Jan 1, 1996·Journal of Gastroenterology and Hepatology·J GeorgeG C Farrell
Jul 17, 1998·Frontiers in Neuroendocrinology·A M Poisner

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