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. 2002 Feb 15;362(Pt 1):13–21. doi: 10.1042/0264-6021:3620013

Reciprocal regulation of capacitative and non-capacitative Ca2+ entry in A7r5 vascular smooth muscle cells: only the latter operates during receptor activation.

Zahid Moneer 1, Colin W Taylor 1
PMCID: PMC1222355  PMID: 11829735

Abstract

In A7r5 vascular smooth muscle cells, Arg(8)-vasopressin (AVP) stimulates phospholipase C leading to activation of two distinct Ca(2+) entry pathways. The capacitative Ca(2+) entry (CCE) pathway is activated by depletion of Ca(2+) stores, is permeable to Mn(2+), Ba(2+) and Ca(2+), and is selectively blocked by Gd(3+)(1 microM). A7r5 cells also express a non-capacitative Ca(2+) entry (NCCE) pathway, which is activated by arachidonic acid that is released by the sequential activities of phospholipase C and diacylglycerol lipase. This pathway is permeable to Sr(2+), Ba(2+) and Ca(2+) and selectively blocked by (R,S)-(3,4-dihydro-6,7-dimethoxy-isochinolin-1-yl)-2-phenyl-N,N-di[2-(2,3,4-trimethoxyphenyl)ethyl]acetamid mesylate ("LOE-908"). We use these selective tools to show that AVP, via the same signalling pathway that leads to activation of NCCE, also inhibits CCE and that the inhibition is not due to depolarization of the plasma membrane. Using the selective inhibitors to resolve the contributions of each Ca(2+) entry pathway during stimulation with AVP, we establish that reciprocal regulation of CCE and NCCE by arachidonic acid ensures that only NCCE is active in the presence of AVP, whereas CCE is active only after its removal. NCCE and CCE are therefore activated in a strict temporal sequence: NCCE first and then CCE. Because Ca(2+) passing through different Ca(2+) entry pathways can selectively regulate different responses, reciprocal regulation of CCE and NCCE may allow a stimulus to first evoke a response and then recruit actively a different response when the stimulus is removed.

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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. 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]
  3. Berridge M. J. Elementary and global aspects of calcium signalling. J Physiol. 1997 Mar 1;499(Pt 2):291–306. doi: 10.1113/jphysiol.1997.sp021927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Broad L. M., Cannon T. R., Short A. D., Taylor C. W. Receptors linked to polyphosphoinositide hydrolysis stimulate Ca2+ extrusion by a phospholipase C-independent mechanism. Biochem J. 1999 Aug 15;342(Pt 1):199–206. [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Byron K. L., Taylor C. W. Spontaneous Ca2+ spiking in a vascular smooth muscle cell line is independent of the release of intracellular Ca2+ stores. J Biol Chem. 1993 Apr 5;268(10):6945–6952. [PubMed] [Google Scholar]
  7. Byron K. L. Vasopressin stimulates Ca2+ spiking activity in A7r5 vascular smooth muscle cells via activation of phospholipase A2. Circ Res. 1996 May;78(5):813–820. doi: 10.1161/01.res.78.5.813. [DOI] [PubMed] [Google Scholar]
  8. Byron K., Taylor C. W. Vasopressin stimulation of Ca2+ mobilization, two bivalent cation entry pathways and Ca2+ efflux in A7r5 rat smooth muscle cells. J Physiol. 1995 Jun 1;485(Pt 2):455–468. doi: 10.1113/jphysiol.1995.sp020742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Fagan K. A., Mons N., Cooper D. M. Dependence of the Ca2+-inhibitable adenylyl cyclase of C6-2B glioma cells on capacitative Ca2+ entry. J Biol Chem. 1998 Apr 10;273(15):9297–9305. doi: 10.1074/jbc.273.15.9297. [DOI] [PubMed] [Google Scholar]
  11. Kawanabe Y., Okamoto Y., Hashimoto N., Masaki T. Characterization of Ca(2+) channels involved in endothelin-1-induced mitogenic responses in vascular smooth muscle cells. Eur J Pharmacol. 2001 Jun 22;422(1-3):15–21. doi: 10.1016/s0014-2999(01)01052-4. [DOI] [PubMed] [Google Scholar]
  12. Khakh B. S., Zhou X., Sydes J., Galligan J. J., Lester H. A. State-dependent cross-inhibition between transmitter-gated cation channels. Nature. 2000 Jul 27;406(6794):405–410. doi: 10.1038/35019066. [DOI] [PubMed] [Google Scholar]
  13. Lin S., Fagan K. A., Li K. X., Shaul P. W., Cooper D. M., Rodman D. M. Sustained endothelial nitric-oxide synthase activation requires capacitative Ca2+ entry. J Biol Chem. 2000 Jun 16;275(24):17979–17985. doi: 10.1074/jbc.275.24.17979. [DOI] [PubMed] [Google Scholar]
  14. Loesch A., Burnstock G. Ultrastructural localization of nitric oxide synthase and endothelin in coronary and pulmonary arteries of newborn rats. Cell Tissue Res. 1995 Mar;279(3):475–483. doi: 10.1007/BF00318161. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Luo D., Broad L. M., Bird G. S., Putney J. W., Jr Signaling pathways underlying muscarinic receptor-induced [Ca2+]i oscillations in HEK293 cells. J Biol Chem. 2000 Nov 28;276(8):5613–5621. doi: 10.1074/jbc.M007524200. [DOI] [PubMed] [Google Scholar]
  17. Manning M., Lammek B., Kolodziejczyk A. M., Seto J., Sawyer W. H. Synthetic antagonists of in vivo antidiuretic and vasopressor responses to arginine-vasopressin. J Med Chem. 1981 Jun;24(6):701–706. doi: 10.1021/jm00138a012. [DOI] [PubMed] [Google Scholar]
  18. McCarron J. G., Flynn E. R., Bradley K. N., Muir T. C. Two Ca2+ entry pathways mediate InsP3-sensitive store refilling in guinea-pig colonic smooth muscle. J Physiol. 2000 May 15;525(Pt 1):113–124. doi: 10.1111/j.1469-7793.2000.00113.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Migas I., Severson D. L. Diacylglycerols derived from membrane phospholipids are metabolized by lipases in A10 smooth muscle cells. Am J Physiol. 1996 Oct;271(4 Pt 1):C1194–C1202. doi: 10.1152/ajpcell.1996.271.4.C1194. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Morgan A. J., Jacob R. Ionomycin enhances Ca2+ influx by stimulating store-regulated cation entry and not by a direct action at the plasma membrane. Biochem J. 1994 Jun 15;300(Pt 3):665–672. doi: 10.1042/bj3000665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Munaron L., Antoniotti S., Distasi C., Lovisolo D. Arachidonic acid mediates calcium influx induced by basic fibroblast growth factor in Balb-c 3T3 fibroblasts. Cell Calcium. 1997 Sep;22(3):179–188. doi: 10.1016/s0143-4160(97)90011-7. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Rogalski S. L., Chavkin C. Eicosanoids inhibit the G-protein-gated inwardly rectifying potassium channel (Kir3) at the Na+/PIP2 gating site. J Biol Chem. 2001 Feb 7;276(18):14855–14860. doi: 10.1074/jbc.M010097200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Stevens T. Is there a role for store-operated calcium entry in vasoconstriction? Am J Physiol Lung Cell Mol Physiol. 2001 May;280(5):L866–L869. doi: 10.1152/ajplung.2001.280.5.L866. [DOI] [PubMed] [Google Scholar]
  29. Thibonnier M., Bayer A. L., Simonson M. S., Kester M. Multiple signaling pathways of V1-vascular vasopressin receptors of A7r5 cells. Endocrinology. 1991 Dec;129(6):2845–2856. doi: 10.1210/endo-129-6-2845. [DOI] [PubMed] [Google Scholar]
  30. Zhang J., Sato M., Duzic E., Kubalak S. W., Lanier S. M., Webb J. G. Adenylyl cyclase isoforms and vasopressin enhancement of agonist-stimulated cAMP in vascular smooth muscle cells. Am J Physiol. 1997 Aug;273(2 Pt 2):H971–H980. doi: 10.1152/ajpheart.1997.273.2.H971. [DOI] [PubMed] [Google Scholar]

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