This Article Full Text Full Text (PDF) All Versions of this Article: 50/4/737    most recent HYPERTENSIONAHA.107.095158v1 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ortiz-Capisano, M. C. Articles by Beierwaltes, W. H. Search for Related Content PubMed PubMed Citation Articles by Ortiz-Capisano, M. C. Articles by Beierwaltes, W. H. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Related Collections ACE/Angiotension receptors Other Research

(Hypertension. 2007;50:737.)
© 2007 American Heart Association, Inc.

XVIIth Scientific Meeting of the Inter-American Society of Hypertension

Expression and Function of the Calcium-Sensing Receptor in Juxtaglomerular Cells

M. Cecilia Ortiz-Capisano; Pablo A. Ortiz; Jeffrey L. Garvin; Pamela Harding; William H. Beierwaltes

From the Department of Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich.

Correspondence to William H. Beierwaltes, Henry Ford Health System, 7121 E&R Building, 2799 W Grand Blvd, Detroit, MI 48202. E-mail wbeierw1{at}hfhs.org

Calcium-sensing receptors sense and translate micromolar changes of extracellular calcium into changes in intracellular calcium. Renin, a component of the renin-angiotensin system, is synthesized by, stored in, and released from the juxtaglomerular cells through a cAMP-dependent pathway. Increased intracellular calcium inhibits the adenylyl cyclase isoform type V, cAMP formation, and renin release from juxtaglomerular cells. We hypothesized that calcium-sensing receptors are expressed in juxtaglomerular cells and mediate changes in intracellular calcium and renin release. To test this we used primary cultures of isolated mouse juxtaglomerular cells in which we ran RT-PCR, Western blots, and immunofluorescence. RT-PCR showed a positive band at the expected 151 bp consistent with calcium-sensing receptor. Western blots showed a 130- to 150-kDa band confirming the calcium-sensing receptor in juxtaglomerular cells. Immunofluorescence and confocal microscopy using 2 different antibodies against the calcium-sensing receptor in juxtaglomerular cells showed positive fluorescence in the juxtaglomerular cells, which also had positive labeling for renin. To test whether calcium-sensing receptors regulate renin release, juxtaglomerular cells were incubated with a calcium-sensing receptor agonist, the calcimimetic cinacalcet-HCl, at concentrations of 50 and 1000 nmol/L in 0.25 mmol/L of calcium medium. Cinacalcet-HCl decreased juxtaglomerular cell cAMP formation to 47.3±6.8% and 44.2±9.7% of basal, respectively (P<0.001), and decreased renin release from 541.9±86.2 to 364.6±64.1 (P<0.05) and 279.6±56.9 (P<0.005) ng of angiotensin I per milliliter per hour per milligram of protein, respectively. We conclude that juxtaglomerular cells express the calcium-sensing receptor and that their activation leads to inhibition of adenylyl cyclase-V activity, decreasing cAMP formation and suppressing renin release.

Key Words: renin • calcium-sensing receptor • cAMP • calcium • juxtaglomerular cells

This article has been cited by other articles:

				M. C. Ortiz-Capisano, T.-D. Liao, P. A. Ortiz, and W. H. Beierwaltes Calcium-dependent phosphodiesterase 1C inhibits renin release from isolated juxtaglomerular cells Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1469 - R1476. [Abstract] [Full Text] [PDF]

				V. E. Torres Type II Calcimimetics and Polycystic Kidney Disease: Unanswered Questions J. Am. Soc. Nephrol., July 1, 2009; 20(7): 1421 - 1425. [Full Text] [PDF]

				E. Ritz How Little Aldosterone is Able to Raise Blood Pressure? Clin. J. Am. Soc. Nephrol., April 1, 2009; 4(4): 703 - 710. [Full Text] [PDF]

				S. Smajilovic and J. Tfelt-Hansen Novel Role of the Calcium-Sensing Receptor in Blood Pressure Modulation Hypertension, December 1, 2008; 52(6): 994 - 1000. [Full Text] [PDF]