Abstract
The role of heterotrimeric GTP-binding proteins in the process of store-operated Ca2+ inflow in hepatocytes was investigated by testing the ability of pertussis toxin to inhibit thapsigargin- and 2,5-di-tert-butylhydroquinone (DBHQ)-induced bivalent cation inflow. Hepatocytes isolated from rats treated with pertussis toxin for 24 h exhibited markedly inhibited rates of both Ca2+ and Mn2+ inflow when these were stimulated by vasopressin, angiotension II, epidermal growth factor, thapsigargin and DBHQ. Pertussis toxin had little effect on the basal intracellular free Ca2+ concentration ([Ca2+]i), basal rates of Ca2+ and Mn2+ inflow, the abilities of vasopressin, angiotensin II, thapsigargin and DBHQ to induce the release of Ca2+ from intracellular stores, and the maximum value of [Ca2+]i reached following agonist-induced release of Ca2+ from intracellular stores. It is concluded that store-operated Ca2+ inflow in hepatocytes employs a slowly ADP-ribosylated trimeric GTP-binding protein and is the physiological mechanism, or one of the physiological mechanisms, by which vasopressin and angiotensin stimulate plasma membrane Ca2+ inflow in this cell type.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barritt G. J., Hughes B. P. The nature and mechanism of activation of the hepatocyte receptor-activated Ca2+ inflow system. Cell Signal. 1991;3(4):283–292. doi: 10.1016/0898-6568(91)90056-z. [DOI] [PubMed] [Google Scholar]
- Berven L. A., Hughes B. P., Barritt G. J. A slowly ADP-ribosylated pertussis-toxin-sensitive GTP-binding regulatory protein is required for vasopressin-stimulated Ca2+ inflow in hepatocytes. Biochem J. 1994 Apr 15;299(Pt 2):399–407. doi: 10.1042/bj2990399. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bird G. S., Putney J. W., Jr Inhibition of thapsigargin-induced calcium entry by microinjected guanine nucleotide analogues. Evidence for the involvement of a small G-protein in capacitative calcium entry. J Biol Chem. 1993 Oct 15;268(29):21486–21488. [PubMed] [Google Scholar]
- Blitzer R. D., Omri G., De Vivo M., Carty D. J., Premont R. T., Codina J., Birnbaumer L., Cotecchia S., Caron M. G., Lefkowitz R. J. Coupling of the expressed alpha 1B-adrenergic receptor to the phospholipase C pathway in Xenopus oocytes. The role of Go. J Biol Chem. 1993 Apr 5;268(10):7532–7537. [PubMed] [Google Scholar]
- Bushfield M., Griffiths S. L., Murphy G. J., Pyne N. J., Knowler J. T., Milligan G., Parker P. J., Mollner S., Houslay M. D. Diabetes-induced alterations in the expression, functioning and phosphorylation state of the inhibitory guanine nucleotide regulatory protein Gi-2 in hepatocytes. Biochem J. 1990 Oct 15;271(2):365–372. doi: 10.1042/bj2710365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crofts J. N., Barritt G. J. The liver cell plasma membrane Ca2+ inflow systems exhibit a broad specificity for divalent metal ions. Biochem J. 1990 Aug 1;269(3):579–587. doi: 10.1042/bj2690579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crofts J. N., Barritt G. J. The measurement of Ca2+ inflow across the liver cell plasma membrane by using quin2 and studies of the roles of Na+ and extracellular Ca2+ in the mechanism of Ca2+ inflow. Biochem J. 1989 Nov 15;264(1):61–70. doi: 10.1042/bj2640061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fasolato C., Hoth M., Penner R. A GTP-dependent step in the activation mechanism of capacitative calcium influx. J Biol Chem. 1993 Oct 5;268(28):20737–20740. [PubMed] [Google Scholar]
- Fernando K. C., Barritt G. J. Characterisation of the inhibition of the hepatocyte receptor-activated Ca2+ inflow system by gadolinium and SK&F 96365. Biochim Biophys Acta. 1994 Jul 21;1222(3):383–389. doi: 10.1016/0167-4889(94)90044-2. [DOI] [PubMed] [Google Scholar]
- Glennon M. C., Bird G. S., Kwan C. Y., Putney J. W., Jr Actions of vasopressin and the Ca(2+)-ATPase inhibitor, thapsigargin, on Ca2+ signaling in hepatocytes. J Biol Chem. 1992 Apr 25;267(12):8230–8233. [PubMed] [Google Scholar]
- Gollasch M., Kleuss C., Hescheler J., Wittig B., Schultz G. Gi2 and protein kinase C are required for thyrotropin-releasing hormone-induced stimulation of voltage-dependent Ca2+ channels in rat pituitary GH3 cells. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6265–6269. doi: 10.1073/pnas.90.13.6265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hallam T. J., Rink T. J. Agonists stimulate divalent cation channels in the plasma membrane of human platelets. FEBS Lett. 1985 Jul 8;186(2):175–179. doi: 10.1016/0014-5793(85)80703-1. [DOI] [PubMed] [Google Scholar]
- Hansen C. A., Yang L. J., Williamson J. R. Mechanisms of receptor-mediated Ca2+ signaling in rat hepatocytes. J Biol Chem. 1991 Oct 5;266(28):18573–18579. [PubMed] [Google Scholar]
- Hughes B. P., Crofts J. N., Auld A. M., Read L. C., Barritt G. J. Evidence that a pertussis-toxin-sensitive substrate is involved in the stimulation by epidermal growth factor and vasopressin of plasma-membrane Ca2+ inflow in hepatocytes. Biochem J. 1987 Dec 15;248(3):911–918. doi: 10.1042/bj2480911. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaconi M. E., Lew D. P., Monod A., Krause K. H. The regulation of store-dependent Ca2+ influx in HL-60 granulocytes involves GTP-sensitive elements. J Biol Chem. 1993 Dec 15;268(35):26075–26078. [PubMed] [Google Scholar]
- Johnson R. M., Connelly P. A., Sisk R. B., Pobiner B. F., Hewlett E. L., Garrison J. C. Pertussis toxin or phorbol 12-myristate 13-acetate can distinguish between epidermal growth factor- and angiotensin-stimulated signals in hepatocytes. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2032–2036. doi: 10.1073/pnas.83.7.2032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kass G. E., Duddy S. K., Moore G. A., Orrenius S. 2,5-Di-(tert-butyl)-1,4-benzohydroquinone rapidly elevates cytosolic Ca2+ concentration by mobilizing the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool. J Biol Chem. 1989 Sep 15;264(26):15192–15198. [PubMed] [Google Scholar]
- Kass G. E., Llopis J., Chow S. C., Duddy S. K., Orrenius S. Receptor-operated calcium influx in rat hepatocytes. Identification and characterization using manganese. J Biol Chem. 1990 Oct 15;265(29):17486–17492. [PubMed] [Google Scholar]
- Komori S., Kawai M., Takewaki T., Ohashi H. GTP-binding protein involvement in membrane currents evoked by carbachol and histamine in guinea-pig ileal muscle. J Physiol. 1992 May;450:105–126. doi: 10.1113/jphysiol.1992.sp019118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krautwurst D., Seifert R., Hescheler J., Schultz G. Formyl peptides and ATP stimulate Ca2+ and Na+ inward currents through non-selective cation channels via G-proteins in dibutyryl cyclic AMP-differentiated HL-60 cells. Involvement of Ca2+ and Na+ in the activation of beta-glucuronidase release and superoxide production. Biochem J. 1992 Dec 15;288(Pt 3):1025–1035. doi: 10.1042/bj2881025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liang M. N., Garrison J. C. The epidermal growth factor receptor is coupled to a pertussis toxin-sensitive guanine nucleotide regulatory protein in rat hepatocytes. J Biol Chem. 1991 Jul 15;266(20):13342–13349. [PubMed] [Google Scholar]
- Liang M., Garrison J. C. Epidermal growth factor activates phospholipase C in rat hepatocytes via a different mechanism from that in A431 or rat1hER cells. Mol Pharmacol. 1992 Nov;42(5):743–752. [PubMed] [Google Scholar]
- Lidofsky S. D., Xie M. H., Sostman A., Scharschmidt B. F., Fitz J. G. Vasopressin increases cytosolic sodium concentration in hepatocytes and activates calcium influx through cation-selective channels. J Biol Chem. 1993 Jul 15;268(20):14632–14636. [PubMed] [Google Scholar]
- Llopis J., Kass G. E., Gahm A., Orrenius S. Evidence for two pathways of receptor-mediated Ca2+ entry in hepatocytes. Biochem J. 1992 May 15;284(Pt 1):243–247. doi: 10.1042/bj2840243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lynch C. J., Prpic V., Blackmore P. F., Exton J. H. Effect of islet-activating pertussis toxin on the binding characteristics of Ca2+-mobilizing hormones and on agonist activation of phosphorylase in hepatocytes. Mol Pharmacol. 1986 Feb;29(2):196–203. [PubMed] [Google Scholar]
- McCarthy S. A., Bicknell R. Responses of pertussis toxin-treated microvascular endothelial cells to transforming growth factor beta 1. No evidence for pertussis-sensitive G-protein involvement in TGF-beta signal transduction. J Biol Chem. 1992 Oct 25;267(30):21617–21622. [PubMed] [Google Scholar]
- Moore G. A., McConkey D. J., Kass G. E., O'Brien P. J., Orrenius S. 2,5-Di(tert-butyl)-1,4-benzohydroquinone--a novel inhibitor of liver microsomal Ca2+ sequestration. FEBS Lett. 1987 Nov 30;224(2):331–336. doi: 10.1016/0014-5793(87)80479-9. [DOI] [PubMed] [Google Scholar]
- Neylon C. B., Nickashin A., Little P. J., Tkachuk V. A., Bobik A. Thrombin-induced Ca2+ mobilization in vascular smooth muscle utilizes a slowly ribosylating pertussis toxin-sensitive G protein. Evidence for the involvement of a G protein in inositol trisphosphate-dependent Ca2+ release. J Biol Chem. 1992 Apr 15;267(11):7295–7302. [PubMed] [Google Scholar]
- Pobiner B. F., Northup J. K., Bauer P. H., Fraser E. D., Garrison J. C. Inhibitory GTP-binding regulatory protein Gi3 can couple angiotensin II receptors to inhibition of adenylyl cyclase in hepatocytes. Mol Pharmacol. 1991 Aug;40(2):156–167. [PubMed] [Google Scholar]
- Putney J. W., Jr A model for receptor-regulated calcium entry. Cell Calcium. 1986 Feb;7(1):1–12. doi: 10.1016/0143-4160(86)90026-6. [DOI] [PubMed] [Google Scholar]
- 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]
- Strazzari M. J., Hughes B. P. Evidence that the Ca2+ inflow pathway in hepatocytes stimulated by thapsigargin is similar to that activated by vasopressin. Biochem Pharmacol. 1993 May 25;45(10):2163–2165. doi: 10.1016/0006-2952(93)90032-r. [DOI] [PubMed] [Google Scholar]
- Takemura H., Hughes A. R., Thastrup O., Putney J. W., Jr Activation of calcium entry by the tumor promoter thapsigargin in parotid acinar cells. Evidence that an intracellular calcium pool and not an inositol phosphate regulates calcium fluxes at the plasma membrane. J Biol Chem. 1989 Jul 25;264(21):12266–12271. [PubMed] [Google Scholar]
- Taylor S. J., Chae H. Z., Rhee S. G., Exton J. H. Activation of the beta 1 isozyme of phospholipase C by alpha subunits of the Gq class of G proteins. Nature. 1991 Apr 11;350(6318):516–518. doi: 10.1038/350516a0. [DOI] [PubMed] [Google Scholar]
- Tsien R. Y., Pozzan T., Rink T. J. Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J Cell Biol. 1982 Aug;94(2):325–334. doi: 10.1083/jcb.94.2.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yang L. J., Baffy G., Rhee S. G., Manning D., Hansen C. A., Williamson J. R. Pertussis toxin-sensitive Gi protein involvement in epidermal growth factor-induced activation of phospholipase C-gamma in rat hepatocytes. J Biol Chem. 1991 Nov 25;266(33):22451–22458. [PubMed] [Google Scholar]
- Yang L., Camoratto A. M., Baffy G., Raj S., Manning D. R., Williamson J. R. Epidermal growth factor-mediated signaling of G(i)-protein to activation of phospholipases in rat-cultured hepatocytes. J Biol Chem. 1993 Feb 15;268(5):3739–3746. [PubMed] [Google Scholar]