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. 1999 Aug 15;342(Pt 1):199–206.

Receptors linked to polyphosphoinositide hydrolysis stimulate Ca2+ extrusion by a phospholipase C-independent mechanism.

L M Broad 1, T R Cannon 1, A D Short 1, C W Taylor 1
PMCID: PMC1220453  PMID: 10432317

Abstract

In A7r5 cells with empty intracellular Ca(2+) stores in which the cytosolic free Ca(2+) concentration ([Ca(2+)](i)) had been increased by capacitative Ca(2+) entry, stimulation of receptors linked to phospholipase C (PLC), including those for Arg(8)-vasopressin (AVP) and platelet-derived growth factor (PDGF), caused a decrease in [Ca(2+)](i.) This effect was further examined in a stable variant of the A7r5 cell line in which the usual ability of hormones to stimulate non-capacitative Ca(2+) entry is not expresssed. In thapsigargin-treated cells, neither AVP nor PDGF affected capacitative Mn(2+) or Ba(2+) entry, but both stimulated the rate of Ca(2+) extrusion, and their abilities to decrease [Ca(2+)](i) were only partially inhibited by removal of extracellular Na(+). These results suggest that receptors linked to PLC also stimulate plasma membrane Ca(2+) pumps. Activation of protein kinase C by phorbol 12, 13-dibutyrate (PDBu, 1 microM) also caused a decrease in [Ca(2+)](i) by accelerating Ca(2+) removal from the cytosol; the effect was again only partially inhibited by removal of extracellular Na(+). An inhibitor of PKC, Ro31-8220 (10 microM), abolished the ability of PDBu to decrease [Ca(2+)](i), without affecting the response to maximal or submaximal concentrations of AVP. Similar experiments with PDGF were impracticable because Ro31-8220, presumably by inhibiting the tyrosine kinase activity of the PDGF receptor, abolished all responses to PDGF. U73122 (10 microM), an inhibitor of PLC, completely inhibited PDGF- or AVP-evoked Ca(2+) mobilization, without preventing either stimulus from causing a decrease in [Ca(2+)](i). We conclude that receptors coupled to PLC, whether via G-proteins or protein tyrosine kinase activity, also share an ability to stimulate the plasma membrane Ca(2+) pump via a mechanism that does not require PLC activity.

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Selected References

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  1. Balasubramanyam M., Gardner J. P. Protein kinase C modulates cytosolic free calcium by stimulating calcium pump activity in Jurkat T cells. Cell Calcium. 1995 Dec;18(6):526–541. doi: 10.1016/0143-4160(95)90015-2. [DOI] [PubMed] [Google Scholar]
  2. Berridge M. J., Bootman M. D., Lipp P. Calcium--a life and death signal. Nature. 1998 Oct 15;395(6703):645–648. doi: 10.1038/27094. [DOI] [PubMed] [Google Scholar]
  3. Berridge M. J. Capacitative calcium entry. Biochem J. 1995 Nov 15;312(Pt 1):1–11. doi: 10.1042/bj3120001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berridge M. J. Inositol trisphosphate and calcium signalling. Nature. 1993 Jan 28;361(6410):315–325. doi: 10.1038/361315a0. [DOI] [PubMed] [Google Scholar]
  5. Berven L. A., Barritt G. J. Evidence obtained using single hepatocytes for inhibition by the phospholipase C inhibitor U73122 of store-operated Ca2+ inflow. Biochem Pharmacol. 1995 May 17;49(10):1373–1379. doi: 10.1016/0006-2952(95)00050-a. [DOI] [PubMed] [Google Scholar]
  6. Birnbaumer L., Zhu X., Jiang M., Boulay G., Peyton M., Vannier B., Brown D., Platano D., Sadeghi H., Stefani E. On the molecular basis and regulation of cellular capacitative calcium entry: roles for Trp proteins. Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15195–15202. doi: 10.1073/pnas.93.26.15195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Brown G. R., Benyon S. L., Kirk C. J., Wictome M., East J. M., Lee A. G., Michelangeli F. Characterisation of a novel Ca2+ pump inhibitor (bis-phenol) and its effects on intracellular Ca2+ mobilization. Biochim Biophys Acta. 1994 Nov 2;1195(2):252–258. doi: 10.1016/0005-2736(94)90264-x. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Carafoli E. Biogenesis: plasma membrane calcium ATPase: 15 years of work on the purified enzyme. FASEB J. 1994 Oct;8(13):993–1002. [PubMed] [Google Scholar]
  12. Carafoli E. Calcium pump of the plasma membrane. Physiol Rev. 1991 Jan;71(1):129–153. doi: 10.1152/physrev.1991.71.1.129. [DOI] [PubMed] [Google Scholar]
  13. Caramelo C., Tsai P., Schrier R. W. Mechanism of cellular effect of phorbol esters on action of arginine vasopressin and angiotensin II on rat vascular smooth muscle cells in culture. Biochem J. 1988 Sep 15;254(3):625–629. doi: 10.1042/bj2540625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Clementi E., Meldolesi J. Pharmacological and functional properties of voltage-independent Ca2+ channels. Cell Calcium. 1996 Apr;19(4):269–279. doi: 10.1016/s0143-4160(96)90068-8. [DOI] [PubMed] [Google Scholar]
  15. De Moel M. P., Van de Put F. H., Vermegen T. M., De Pont J. H., Willems P. H. Effect of the aminosteroid, U73122, on Ca2+ uptake and release properties of rat liver microsomes. Eur J Biochem. 1995 Dec 1;234(2):626–631. doi: 10.1111/j.1432-1033.1995.626_b.x. [DOI] [PubMed] [Google Scholar]
  16. Duddy S. K., Kass G. E., Orrenius S. Ca2(+)-mobilizing hormones stimulate Ca2+ efflux from hepatocytes. J Biol Chem. 1989 Dec 15;264(35):20863–20866. [PubMed] [Google Scholar]
  17. Green A. K., Cobbold P. H., Dixon C. J. Effects on the hepatocyte [Ca2+]i oscillator of inhibition of the plasma membrane Ca2+ pump by carboxyeosin or glucagon-(19-29). Cell Calcium. 1997 Aug;22(2):99–109. doi: 10.1016/s0143-4160(97)90110-x. [DOI] [PubMed] [Google Scholar]
  18. Helliwell R. M., Large W. A. Alpha 1-adrenoceptor activation of a non-selective cation current in rabbit portal vein by 1,2-diacyl-sn-glycerol. J Physiol. 1997 Mar 1;499(Pt 2):417–428. doi: 10.1113/jphysiol.1997.sp021938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Iwamoto T., Wakabayashi S., Shigekawa M. Growth factor-induced phosphorylation and activation of aortic smooth muscle Na+/Ca2+ exchanger. J Biol Chem. 1995 Apr 14;270(15):8996–9001. doi: 10.1074/jbc.270.15.8996. [DOI] [PubMed] [Google Scholar]
  20. Kimes B. W., Brandt B. L. Characterization of two putative smooth muscle cell lines from rat thoracic aorta. Exp Cell Res. 1976 Mar 15;98(2):349–366. doi: 10.1016/0014-4827(76)90446-8. [DOI] [PubMed] [Google Scholar]
  21. Loirand G., Pacaud P., Baron A., Mironneau C., Mironneau J. Large conductance calcium-activated non-selective cation channel in smooth muscle cells isolated from rat portal vein. J Physiol. 1991 Jun;437:461–475. doi: 10.1113/jphysiol.1991.sp018606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lückhoff A., Clapham D. E. Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca(2+)-permeable channel. Nature. 1992 Jan 23;355(6358):356–358. doi: 10.1038/355356a0. [DOI] [PubMed] [Google Scholar]
  23. Mikoshiba K. The InsP3 receptor and intracellular Ca2+ signaling. Curr Opin Neurobiol. 1997 Jun;7(3):339–345. doi: 10.1016/s0959-4388(97)80061-x. [DOI] [PubMed] [Google Scholar]
  24. Monteith G. R., Roufogalis B. D. The plasma membrane calcium pump--a physiological perspective on its regulation. Cell Calcium. 1995 Dec;18(6):459–470. doi: 10.1016/0143-4160(95)90009-8. [DOI] [PubMed] [Google Scholar]
  25. Montell C. New light on TRP and TRPL. Mol Pharmacol. 1997 Nov;52(5):755–763. doi: 10.1124/mol.52.5.755. [DOI] [PubMed] [Google Scholar]
  26. Muallem S., Pandol S. J., Beeker T. G. Calcium mobilizing hormones activate the plasma membrane Ca2+ pump of pancreatic acinar cells. J Membr Biol. 1988 Nov;106(1):57–69. doi: 10.1007/BF01871767. [DOI] [PubMed] [Google Scholar]
  27. Oike M., Kitamura K., Kuriyama H. Protein kinase C activates the non-selective cation channel in the rabbit portal vein. Pflugers Arch. 1993 Jul;424(2):159–164. doi: 10.1007/BF00374607. [DOI] [PubMed] [Google Scholar]
  28. Perianin A., Synderman R. Analysis of calcium homeostasis in activated human polymorphonuclear leukocytes. Evidence for two distinct mechanisms for lowering cytosolic calcium. J Biol Chem. 1989 Jan 15;264(2):1005–1009. [PubMed] [Google Scholar]
  29. Plevin R., Stewart A., Paul A., Wakelam M. J. Vasopressin-stimulated [3H]-inositol phosphate and [3H]-phosphatidylbutanol accumulation in A10 vascular smooth muscle cells. Br J Pharmacol. 1992 Sep;107(1):109–115. doi: 10.1111/j.1476-5381.1992.tb14471.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Putney J. W., Jr Capacitative calcium entry revisited. Cell Calcium. 1990 Nov-Dec;11(10):611–624. doi: 10.1016/0143-4160(90)90016-n. [DOI] [PubMed] [Google Scholar]
  31. Randriamampita C., Trautmann A. Arachidonic acid activates Ca2+ extrusion in macrophages. J Biol Chem. 1990 Oct 25;265(30):18059–18062. [PubMed] [Google Scholar]
  32. Rink T. J., Sage S. O. Stimulated calcium efflux from fura-2-loaded human platelets. J Physiol. 1987 Dec;393:513–524. doi: 10.1113/jphysiol.1987.sp016837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rizzuto R., Brini M., Murgia M., Pozzan T. Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria. Science. 1993 Oct 29;262(5134):744–747. doi: 10.1126/science.8235595. [DOI] [PubMed] [Google Scholar]
  34. Taylor C. W., Traynor D. Calcium and inositol trisphosphate receptors. J Membr Biol. 1995 May;145(2):109–118. doi: 10.1007/BF00237369. [DOI] [PubMed] [Google Scholar]
  35. Taylor C. W. Why do hormones stimulate Ca2+ mobilization? Biochem Soc Trans. 1995 Aug;23(3):637–642. doi: 10.1042/bst0230637. [DOI] [PubMed] [Google Scholar]
  36. Toescu E. C., Petersen O. H. Region-specific activity of the plasma membrane Ca2+ pump and delayed activation of Ca2+ entry characterize the polarized, agonist-evoked Ca2+ signals in exocrine cells. J Biol Chem. 1995 Apr 14;270(15):8528–8535. doi: 10.1074/jbc.270.15.8528. [DOI] [PubMed] [Google Scholar]
  37. Vigne P., Breittmayer J. P., Duval D., Frelin C., Lazdunski M. The Na+/Ca2+ antiporter in aortic smooth muscle cells. Characterization and demonstration of an activation by phorbol esters. J Biol Chem. 1988 Jun 15;263(17):8078–8083. [PubMed] [Google Scholar]
  38. Wolenski J. S. Regulation of calmodulin-binding myosins. Trends Cell Biol. 1995 Aug;5(8):310–316. doi: 10.1016/s0962-8924(00)89053-4. [DOI] [PubMed] [Google Scholar]
  39. Young K. W., Pinnock R. D., Gibson W. J., Young J. M. Dual effects of histamine and substance P on intracellular calcium levels in human U373 MG astrocytoma cells: role of protein kinase C. Br J Pharmacol. 1998 Feb;123(3):545–557. doi: 10.1038/sj.bjp.0701620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zhang B. X., Zhao H., Loessberg P., Muallem S. Activation of the plasma membrane Ca2+ pump during agonist stimulation of pancreatic acini. J Biol Chem. 1992 Aug 5;267(22):15419–15425. [PubMed] [Google Scholar]

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