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. 2003 Mar 1;370(Pt 2):439–448. doi: 10.1042/BJ20021104

Nitric oxide co-ordinates the activities of the capacitative and non-capacitative Ca2+-entry pathways regulated by vasopressin.

Zahid Moneer 1, Jeanette L Dyer 1, Colin W Taylor 1
PMCID: PMC1223200  PMID: 12459038

Abstract

In A7r5 vascular smooth muscle cells vasopressin, via arachidonic acid, regulates two Ca(2+)-entry pathways. Capacitative Ca(2+) entry (CCE), activated by empty Ca(2+) stores, is inhibited by arachidonic acid, and non-capacitative Ca(2+) entry (NCCE) is stimulated by it. This reciprocal regulation ensures that all Ca(2+) entry is via NCCE in the presence of vasopressin, while CCE mediates a transient Ca(2+) 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 Ca(2+) 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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Selected References

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  1. Alonso-Torre S. R., García-Sancho J. Arachidonic acid inhibits capacitative calcium entry in rat thymocytes and human neutrophils. Biochim Biophys Acta. 1997 Sep 4;1328(2):207–213. doi: 10.1016/s0005-2736(97)00094-1. [DOI] [PubMed] [Google Scholar]
  2. Archer S. Measurement of nitric oxide in biological models. FASEB J. 1993 Feb 1;7(2):349–360. doi: 10.1096/fasebj.7.2.8440411. [DOI] [PubMed] [Google Scholar]
  3. Bahnson T. D., Pandol S. J., Dionne V. E. Cyclic GMP modulates depletion-activated Ca2+ entry in pancreatic acinar cells. J Biol Chem. 1993 May 25;268(15):10808–10812. [PubMed] [Google Scholar]
  4. Barritt G. J. Receptor-activated Ca2+ inflow in animal cells: a variety of pathways tailored to meet different intracellular Ca2+ signalling requirements. Biochem J. 1999 Jan 15;337(Pt 2):153–169. [PMC free article] [PubMed] [Google Scholar]
  5. Berridge M. J., Lipp P., Bootman M. D. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol. 2000 Oct;1(1):11–21. doi: 10.1038/35036035. [DOI] [PubMed] [Google Scholar]
  6. Bian X., Bird G. S., Putney J. W., Jr cGMP is not required for capacitative Ca2+ entry in Jurkat T-lymphocytes. Cell Calcium. 1996 Apr;19(4):351–354. doi: 10.1016/s0143-4160(96)90075-5. [DOI] [PubMed] [Google Scholar]
  7. Bischof G., Brenman J., Bredt D. S., Machen T. E. Possible regulation of capacitative Ca2+ entry into colonic epithelial cells by NO and cGMP. Cell Calcium. 1995 Apr;17(4):250–262. doi: 10.1016/0143-4160(95)90071-3. [DOI] [PubMed] [Google Scholar]
  8. Blayney L. M., Gapper P. W., Newby A. C. Inhibition of a receptor-operated calcium channel in pig aortic microsomes by cyclic GMP-dependent protein kinase. Biochem J. 1991 Feb 1;273(Pt 3):803–806. doi: 10.1042/bj2730803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Broad L. M., Cannon T. R., Taylor C. W. A non-capacitative pathway activated by arachidonic acid is the major Ca2+ entry mechanism in rat A7r5 smooth muscle cells stimulated with low concentrations of vasopressin. J Physiol. 1999 May 15;517(Pt 1):121–134. doi: 10.1111/j.1469-7793.1999.0121z.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brophy C. M., Knoepp L., Xin J., Pollock J. S. Functional expression of NOS 1 in vascular smooth muscle. Am J Physiol Heart Circ Physiol. 2000 Mar;278(3):H991–H997. doi: 10.1152/ajpheart.2000.278.3.H991. [DOI] [PubMed] [Google Scholar]
  11. Cardy T. J., Traynor D., Taylor C. W. Differential regulation of types-1 and -3 inositol trisphosphate receptors by cytosolic Ca2+. Biochem J. 1997 Dec 15;328(Pt 3):785–793. doi: 10.1042/bj3280785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Clapham D. E., Runnels L. W., Strübing C. The TRP ion channel family. Nat Rev Neurosci. 2001 Jun;2(6):387–396. doi: 10.1038/35077544. [DOI] [PubMed] [Google Scholar]
  13. Clementi E. Role of nitric oxide and its intracellular signalling pathways in the control of Ca2+ homeostasis. Biochem Pharmacol. 1998 Mar 15;55(6):713–718. doi: 10.1016/s0006-2952(97)00375-4. [DOI] [PubMed] [Google Scholar]
  14. Cohen R. A., Weisbrod R. M., Gericke M., Yaghoubi M., Bierl C., Bolotina V. M. Mechanism of nitric oxide-induced vasodilatation: refilling of intracellular stores by sarcoplasmic reticulum Ca2+ ATPase and inhibition of store-operated Ca2+ influx. Circ Res. 1999 Feb 5;84(2):210–219. doi: 10.1161/01.res.84.2.210. [DOI] [PubMed] [Google Scholar]
  15. Dedkova Elena N., Blatter Lothar A. Nitric oxide inhibits capacitative Ca2+ entry and enhances endoplasmic reticulum Ca2+ uptake in bovine vascular endothelial cells. J Physiol. 2002 Feb 15;539(Pt 1):77–91. doi: 10.1113/jphysiol.2001.013258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fagan K. A., Graf R. A., Tolman S., Schaack J., Cooper D. M. Regulation of a Ca2+-sensitive adenylyl cyclase in an excitable cell. Role of voltage-gated versus capacitative Ca2+ entry. J Biol Chem. 2000 Dec 22;275(51):40187–40194. doi: 10.1074/jbc.M006606200. [DOI] [PubMed] [Google Scholar]
  17. Favre C. J., Ufret-Vincenty C. A., Stone M. R., Ma H. T., Gill D. L. Ca2+ pool emptying stimulates Ca2+ entry activated by S-nitrosylation. J Biol Chem. 1998 Nov 20;273(47):30855–30858. doi: 10.1074/jbc.273.47.30855. [DOI] [PubMed] [Google Scholar]
  18. Garthwaite J., Southam E., Boulton C. L., Nielsen E. B., Schmidt K., Mayer B. Potent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Mol Pharmacol. 1995 Aug;48(2):184–188. [PubMed] [Google Scholar]
  19. Inoue R., Okada T., Onoue H., Hara Y., Shimizu S., Naitoh S., Ito Y., Mori Y. The transient receptor potential protein homologue TRP6 is the essential component of vascular alpha(1)-adrenoceptor-activated Ca(2+)-permeable cation channel. Circ Res. 2001 Feb 16;88(3):325–332. doi: 10.1161/01.res.88.3.325. [DOI] [PubMed] [Google Scholar]
  20. Iwamuro Y., Miwa S., Zhang X. F., Minowa T., Enoki T., Okamoto Y., Hasegawa H., Furutani H., Okazawa M., Ishikawa M. Activation of three types of voltage-independent Ca2+ channel in A7r5 cells by endothelin-1 as revealed by a novel Ca2+ channel blocker LOE 908. Br J Pharmacol. 1999 Mar;126(5):1107–1114. doi: 10.1038/sj.bjp.0702416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jung Silke, Strotmann Rainer, Schultz Günter, Plant Tim D. TRPC6 is a candidate channel involved in receptor-stimulated cation currents in A7r5 smooth muscle cells. Am J Physiol Cell Physiol. 2002 Feb;282(2):C347–C359. doi: 10.1152/ajpcell.00283.2001. [DOI] [PubMed] [Google Scholar]
  22. Luo D., Broad L. M., Bird G. S., Putney J. W., Jr Mutual antagonism of calcium entry by capacitative and arachidonic acid-mediated calcium entry pathways. J Biol Chem. 2001 Mar 23;276(23):20186–20189. doi: 10.1074/jbc.M100327200. [DOI] [PubMed] [Google Scholar]
  23. Ma H. T., Favre C. J., Patterson R. L., Stone M. R., Gill D. L. Ca(2+) entry activated by S-nitrosylation. Relationship to store-operated ca(2+) entry. J Biol Chem. 1999 Dec 10;274(50):35318–35324. doi: 10.1074/jbc.274.50.35318. [DOI] [PubMed] [Google Scholar]
  24. Marletta M. A. Another activation switch for endothelial nitric oxide synthase: why does it have to be so complicated? Trends Biochem Sci. 2001 Sep;26(9):519–521. doi: 10.1016/s0968-0004(01)01937-5. [DOI] [PubMed] [Google Scholar]
  25. Mignen O., Shuttleworth T. J. I(ARC), a novel arachidonate-regulated, noncapacitative Ca(2+) entry channel. J Biol Chem. 2000 Mar 31;275(13):9114–9119. doi: 10.1074/jbc.275.13.9114. [DOI] [PubMed] [Google Scholar]
  26. Mignen O., Thompson J. L., Shuttleworth T. J. Reciprocal regulation of capacitative and arachidonate-regulated noncapacitative Ca2+ entry pathways. J Biol Chem. 2001 Jul 24;276(38):35676–35683. doi: 10.1074/jbc.M105626200. [DOI] [PubMed] [Google Scholar]
  27. Moneer Zahid, Taylor Colin W. Reciprocal regulation of capacitative and non-capacitative Ca2+ entry in A7r5 vascular smooth muscle cells: only the latter operates during receptor activation. Biochem J. 2002 Feb 15;362(Pt 1):13–21. doi: 10.1042/0264-6021:3620013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Putney J. W., Jr TRP, inositol 1,4,5-trisphosphate receptors, and capacitative calcium entry. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14669–14671. doi: 10.1073/pnas.96.26.14669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shuttleworth T. J. Arachidonic acid activates the noncapacitative entry of Ca2+ during [Ca2+]i oscillations. J Biol Chem. 1996 Sep 6;271(36):21720–21725. doi: 10.1074/jbc.271.36.21720. [DOI] [PubMed] [Google Scholar]
  30. Shuttleworth T. J., Thompson J. L. Discriminating between capacitative and arachidonate-activated Ca(2+) entry pathways in HEK293 cells. J Biol Chem. 1999 Oct 29;274(44):31174–31178. doi: 10.1074/jbc.274.44.31174. [DOI] [PubMed] [Google Scholar]
  31. Shuttleworth T. J., Thompson J. L. Evidence for a non-capacitative Ca2+ entry during [Ca2+] oscillations. Biochem J. 1996 Jun 15;316(Pt 3):819–824. doi: 10.1042/bj3160819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stoyanovsky D., Murphy T., Anno P. R., Kim Y. M., Salama G. Nitric oxide activates skeletal and cardiac ryanodine receptors. Cell Calcium. 1997 Jan;21(1):19–29. doi: 10.1016/s0143-4160(97)90093-2. [DOI] [PubMed] [Google Scholar]
  33. Thyagarajan B., Poteser M., Romanin C., Kahr H., Zhu M. X., Groschner K. Expression of Trp3 determines sensitivity of capacitative Ca2+ entry to nitric oxide and mitochondrial Ca2+ handling: evidence for a role of Trp3 as a subunit of capacitative Ca2+ entry channels. J Biol Chem. 2001 Oct 12;276(51):48149–48158. doi: 10.1074/jbc.M103977200. [DOI] [PubMed] [Google Scholar]
  34. Xu L., Eu J. P., Meissner G., Stamler J. S. Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science. 1998 Jan 9;279(5348):234–237. doi: 10.1126/science.279.5348.234. [DOI] [PubMed] [Google Scholar]
  35. Xu X., Star R. A., Tortorici G., Muallem S. Depletion of intracellular Ca2+ stores activates nitric-oxide synthase to generate cGMP and regulate Ca2+ influx. J Biol Chem. 1994 Apr 29;269(17):12645–12653. [PubMed] [Google Scholar]
  36. Zhang X. F., Iwamuro Y., Enoki T., Okazawa M., Lee K., Komuro T., Minowa T., Okamoto Y., Hasegawa H., Furutani H. Pharmacological characterization of Ca2+ entry channels in endothelin-1-induced contraction of rat aorta using LOE 908 and SK&F 96365. Br J Pharmacol. 1999 Jul;127(6):1388–1398. doi: 10.1038/sj.bjp.0702661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. van Rossum D. B., Patterson R. L., Ma H. T., Gill D. L. Ca2+ entry mediated by store depletion, S-nitrosylation, and TRP3 channels. Comparison of coupling and function. J Biol Chem. 2000 Sep 15;275(37):28562–28568. doi: 10.1074/jbc.M003147200. [DOI] [PubMed] [Google Scholar]

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