Cyclosporine A increases renin release from single juxtaglomerular cells in a calcium‐dependent manner

• Published in: The FASEB journal Vol. 20; no. 4; p. A343
• Main Authors: Friis, Ulla Glenert, Jensen, Boye Lagerbon, Skøtt, Ole
• Format: Journal Article
• Language: English
• Published: Federation of American Societies for Experimental Biology 01-03-2006
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.4.A343-a

It is well known that the immunosuppressant cyclosporine A (CsA) stimulates the renin‐angiotensin system, but the mechanism behind remains obscure. Cyclosporine A is an inhibitor of the calcium‐activated phosphatase calcineurin, and it is possible that CsA exerts its effect on renin release through a direct effect in juxtaglomerular (JG)‐cells. The aim of this study was to determine the effect of CsA on renin secretion, using electrophysiological methods on single rat JG cells. Membrane capacitance (Cm) was recorded as a measure of exocytosis. Results: Extracellular application of CsA (5 μM) increased membrane capacitance (Cm) by 10.7% ± 2.9% (n=5; P<0.05). When the experiments were repeated with a PKA‐blocker (RpcAMPs (5 μM)) in the patch pipette, CsA (5 μM) still increased membrane capacitance significantly (15.8% ± 4.2% (n=4)), indicating that the increase in exocytosis is independent on the cAMP‐PKA‐pathway. The effect of CsA could be mimicked by chelating intracellular calcium using EGTA (0.1 mM) in the patch pipette. Under these experimental conditions, membrane capacitance increased 12.4% ± 3% (n=3). Addition of CsA (5 μM) did not result in any further increase in Cm (amounting to 11.8% ± 4.7% (n=3)), indicating a common signal transduction pathway.
Conclusions
Lowering intracellular calcium and cyclosporine A have common effects on Cm which could be due to calcineurin inhibition. In addition, calcineurin exerts a tonic supressor effect on renin release from juxtaglomerular cells.
This study was supported by grants from Carlsbergfondet, the Novo Nordisk Foundation and the Danish Heart Foundation.