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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/R1469    most recent 00121.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ortiz-Capisano, M. C. Articles by Beierwaltes, W. H. PubMed PubMed Citation Articles by Ortiz-Capisano, M. C. Articles by Beierwaltes, W. H.

Articles

Calcium-dependent phosphodiesterase 1C inhibits renin release from isolated juxtaglomerular cells

Department of Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan

Submitted February 25, 2009 ; accepted in final form September 3, 2009

Renin release from the juxtaglomerular (JG) cell is stimulated by the second messenger cAMP and inhibited by calcium. We previously showed JG cells contain a calcium sensing receptor (CaSR), which, when stimulated, decreases cAMP formation and inhibits renin release. We hypothesize CaSR activation decreases cAMP and renin release, in part, by stimulating a calcium calmodulin-activated phosphodiesterase 1 (PDE1). We incubated our primary culture of JG cells with two selective PDE1 inhibitors [8-methoxymethil-IBMX (8-MM-IBMX; 20 µM) and vinpocetine (40 µM)] and the calmodulin inhibitor W-7 (10 µM) and measured cAMP and renin release. Stimulation of the JG cell CaSR with the calcimimetic cinacalcet (1 µM) resulted in decreased cAMP from a basal of 1.13 ± 0.14 to 0.69 ± 0.08 pM/mg protein (P < 0.001) and in renin release from 0.89 ± 0.16 to 0.38 ± 0.08 µg ANG I/ml·h^–1·mg protein^–1 (P < 0.001). However, the addition of 8-MM-IBMX with cinacalcet returned both cAMP (1.10 ± 0.19 pM/mg protein) and renin (0.57 ± 0.16 µg ANG I/ml·h^–1·mg protein^–1) to basal levels. Similar results were obtained with vinpocetine, and also with W-7. Combining 8-MM-IBMX and W-7 had no additive effect. To determine which PDE1 isoform is involved, we performed Western blot analysis for PDE1A, B, and C. Only Western blot analysis for PDE1C showed a characteristic band apparent at 80 kDa. Immunofluorescence showed cytoplasmic distribution of PDE1C and renin in the JG cells. In conclusion, PDE1C is expressed in isolated JG cells, and contributes to calcium's inhibitory modulation of renin release from JG cells.

angiotensin; calmodulin; phosphodiesterase; cAMP; adenylyl cyclase