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(Circulation Research. 2002;90:996.)
© 2002 American Heart Association, Inc.

Cellular Biology

Control of Renin Secretion From Rat Juxtaglomerular Cells by cAMP-Specific Phosphodiesterases

Ulla G. Friis, Boye L. Jensen, Shala Sethi, Ditte Andreasen, Pernille B. Hansen, Ole Skøtt

From the Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark.

Correspondence to Ulla G. Friis, PhD, Physiology and Pharmacology, University of Southern Denmark, Winsloewparken 21, 3. DK-5000 Odense C, Denmark. E-mail friis{at}imbmed.sdu.dk

We tested the hypothesis that cGMP stimulates renin release through inhibition of the cAMP-specific phosphodiesterase 3 (PDE3) in isolated rat juxtaglomerular (JG) cells. In addition, we assessed the involvement of PDE4 in JG-cell function. JG cells expressed PDE3A and PDE3B, and the PDE3 inhibitor trequinsin increased cellular cAMP content, enhanced forskolin-induced cAMP formation, and stimulated renin release from incubated and superfused JG cells. Trequinsin-mediated stimulation of renin release was inhibited by the permeable protein kinase A antagonist Rp-8-CPT-cAMPS. PDE4C was also expressed, and the PDE4 inhibitor rolipram enhanced cellular cAMP content. Dialysis of single JG cells with cAMP in whole-cell patch-clamp experiments led to concentration-dependent, biphasic changes in cell membrane capacitance (C_m) with a marked increase in C_m at 1 µmol/L, no net change at 10 µmol/L, and a decrease at 100 µmol/L cAMP. cGMP also had a dual effect on C_m at 10-fold higher concentration compared with cAMP. Trequinsin, milrinone, and rolipram mimicked the effect of cAMP on C_m. Trequinsin, cAMP, and cGMP enhanced outward current 2- to 3-fold at positive membrane potentials. The effects of cAMP, cGMP, and trequinsin on C_m and cell currents were abolished by inhibition of protein kinase A with Rp-cAMPs. We conclude that degradation of cAMP by PDE3 and PDE4 contributes to regulation of renin release from JG cells. Our data provide evidence at the cellular level that stimulation of renin release by cGMP involves inhibition of PDE3 resulting in enhanced cAMP formation and activation of the cAMP sensitive protein kinase.

Key Words: juxtaglomerular apparatus • renin • exocytosis • cGMP • phosphodiesterase

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