In A7r5 vascular smooth muscle cells vasopressin, via arachidonic acid, regulates two Ca2+-entry pathways. Capacitative Ca2+ entry (CCE), activated by empty Ca2+ stores, is inhibited by arachidonic acid, and non-capacitative Ca2+ entry (NCCE) is stimulated by it. This reciprocal regulation ensures that all Ca2+ entry is via NCCE in the presence of vasopressin, while CCE mediates a transient Ca2+ entry only after removal of vasopressin. We demonstrate that type III NO synthase (NOS III) is expressed in A7r5 cells and that NO inhibits CCE. Inhibition of CCE by vasopressin requires NOS III and the requirement lies downstream of arachidonic acid. Activation of soluble guanylate cyclase by NO and subsequent activation of protein kinase G are required for inhibition of CCE. Stimulation of NCCE by vasopressin also requires NOS III, but the stimulation is neither mimicked by cGMP nor blocked by inhibitors of soluble guanylate cyclase or protein kinase G. We conclude that arachidonic acid formed in response to vasopressin stimulates NOS III. NO then directly stimulates Ca2+ entry through NCCE and, via protein kinase G, it inhibits CCE. The additional amplification provided by the involvement of guanylate cyclase and protein kinase G ensures that CCE will always be inhibited when vasopressin activates NCCE.
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March 2003
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Research Article|
March 01 2003
Nitric oxide co-ordinates the activities of the capacitative and non-capacitative Ca2+-entry pathways regulated by vasopressin
Zahid MONEER;
Zahid MONEER
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Jeanette L. DYER;
Jeanette L. DYER
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Colin W. TAYLOR
Colin W. TAYLOR
1
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
1To whom correspondence should be addressed (e-mail cwt1000@cam.ac.uk).
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Publisher: Portland Press Ltd
Received:
July 11 2002
Revision Received:
November 28 2002
Accepted:
December 02 2002
Accepted Manuscript online:
December 02 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 370 (2): 439–448.
Article history
Received:
July 11 2002
Revision Received:
November 28 2002
Accepted:
December 02 2002
Accepted Manuscript online:
December 02 2002
Citation
Zahid MONEER, Jeanette L. DYER, Colin W. TAYLOR; Nitric oxide co-ordinates the activities of the capacitative and non-capacitative Ca2+-entry pathways regulated by vasopressin. Biochem J 1 March 2003; 370 (2): 439–448. doi: https://doi.org/10.1042/bj20021104
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