Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1988 Jan 1;249(1):135–141. doi: 10.1042/bj2490135

Desensitization and recovery of muscarinic and histaminergic Ca2+ mobilization in 1321N1 astrocytoma cells.

P M McDonough 1, J H Eubanks 1, J H Brown 1
PMCID: PMC1148676  PMID: 3342003

Abstract

Intracellular free Ca2+ was monitored in suspensions of 1321N1 astrocytoma cells by using the Ca2+ indicator fura-2. The cytoplasmic Ca2+ concentration increased from 237 +/- 6 nM to 1580 +/- 170 nM within 3-5 s of addition of 300 microM-carbachol. After the peak in response, the Ca2+ concentration diminished, establishing a new steady state in about 1 min that was approx. 150 nM above the previous baseline. Histamine increased cytoplasmic Ca2+ to about 40% of the maximal value seen with carbachol. In Ca2+-free buffer each agonist elicited a normal initial increase in cytoplasmic Ca2+, but the sustained portion of the response was abolished. The increase in Ca2+ in response to either carbachol or histamine could be completely inhibited by pretreating the cells with carbachol; the response to carbachol could be partially inhibited by pretreating the cells with histamine. The Ca2+ responses did not recover in the continued presence of carbachol. However, if the carbachol was washed out or if atropine was added after carbachol, the responses to agonist recovered in a time-dependent manner (half-time 3-4 min), and recovery depended on the presence of extracellular calcium. The results indicate that carbachol and histamine stimulate release of Ca2+ from the same intracellular Ca2+ store, that depletion of this store is responsible for heterologous desensitization between these two agonists, and that repletion of the agonist-sensitive Ca2+ pool does not occur in the continued presence of agonist or in the absence of extracellular Ca2+.

Full text

PDF
135

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ambler S. K., Thompson B., Solski P. A., Brown J. H., Taylor P. Receptor-mediated inositol phosphate formation in relation to calcium mobilization: a comparison of two cell lines. Mol Pharmacol. 1987 Sep;32(3):376–383. [PubMed] [Google Scholar]
  2. Berridge M. J. Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol. Biochem J. 1983 Jun 15;212(3):849–858. doi: 10.1042/bj2120849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berridge M. J. Regulation of ion channels by inositol trisphosphate and diacylglycerol. J Exp Biol. 1986 Sep;124:323–335. doi: 10.1242/jeb.124.1.323. [DOI] [PubMed] [Google Scholar]
  4. Bréant B., Keppens S., De Wulf H. Heterologous desensitization of the cyclic AMP-independent glycogenolytic response in rat liver cells. Biochem J. 1981 Dec 15;200(3):509–514. doi: 10.1042/bj2000509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carafoli E. Calcium-transporting systems of plasma membranes, with special attention to their regulation. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1984;17:543–549. [PubMed] [Google Scholar]
  6. Chew C. S. Cholecystokinin, carbachol, gastrin, histamine, and forskolin increase [Ca2+]i in gastric glands. Am J Physiol. 1986 Jun;250(6 Pt 1):G814–G823. doi: 10.1152/ajpgi.1986.250.6.G814. [DOI] [PubMed] [Google Scholar]
  7. Evans T., Hepler J. R., Masters S. B., Brown J. H., Harden T. K. Guanine nucleotide regulation of agonist binding to muscarinic cholinergic receptors. Relation to efficacy of agonists for stimulation of phosphoinositide breakdown and Ca2+ mobilization. Biochem J. 1985 Dec 15;232(3):751–757. doi: 10.1042/bj2320751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  9. Harden T. K., Heng M. M., Brown J. H. Receptor reserve in the calcium-dependent cyclic AMP response of astrocytoma cells to muscarinic receptor stimulation: demonstration by agonist-induced desensitization, receptor inactivation, and phorbol ester treatment. Mol Pharmacol. 1986 Sep;30(3):200–206. [PubMed] [Google Scholar]
  10. Irvine R. F., Letcher A. J., Heslop J. P., Berridge M. J. The inositol tris/tetrakisphosphate pathway--demonstration of Ins(1,4,5)P3 3-kinase activity in animal tissues. Nature. 1986 Apr 17;320(6063):631–634. doi: 10.1038/320631a0. [DOI] [PubMed] [Google Scholar]
  11. Irvine R. F., Moor R. M. Micro-injection of inositol 1,3,4,5-tetrakisphosphate activates sea urchin eggs by a mechanism dependent on external Ca2+. Biochem J. 1986 Dec 15;240(3):917–920. doi: 10.1042/bj2400917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Joseph S. K., Coll K. E., Thomas A. P., Rubin R., Williamson J. R. The role of extracellular Ca2+ in the response of the hepatocyte to Ca2+-dependent hormones. J Biol Chem. 1985 Oct 15;260(23):12508–12515. [PubMed] [Google Scholar]
  13. Kuno M., Gardner P. Ion channels activated by inositol 1,4,5-trisphosphate in plasma membrane of human T-lymphocytes. Nature. 1987 Mar 19;326(6110):301–304. doi: 10.1038/326301a0. [DOI] [PubMed] [Google Scholar]
  14. Masters S. B., Harden T. K., Brown J. H. Relationships between phosphoinositide and calcium responses to muscarinic agonists in astrocytoma cells. Mol Pharmacol. 1984 Sep;26(2):149–155. [PubMed] [Google Scholar]
  15. Masters S. B., Quinn M. T., Brown J. H. Agonist-induced desensitization of muscarinic receptor-mediated calcium efflux without concomitant desensitization of phosphoinositide hydrolysis. Mol Pharmacol. 1985 Mar;27(3):325–332. [PubMed] [Google Scholar]
  16. Matsumoto T., Kanaide H., Nishimura J., Shogakiuchi Y., Kobayashi S., Nakamura M. Histamine activates H1-receptors to induce cytosolic free calcium transients in cultured vascular smooth muscle cells from rat aorta. Biochem Biophys Res Commun. 1986 Feb 26;135(1):172–177. doi: 10.1016/0006-291x(86)90958-7. [DOI] [PubMed] [Google Scholar]
  17. Merritt J. E., Rubin R. P. Pancreatic amylase secretion and cytoplasmic free calcium. Effects of ionomycin, phorbol dibutyrate and diacylglycerols alone and in combination. Biochem J. 1985 Aug 15;230(1):151–159. doi: 10.1042/bj2300151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Murphy E., Wheeler D. M., LeFurgey A., Jacob R., Lobaugh L. A., Lieberman M. Coupled sodium-calcium transport in cultured chick heart cells. Am J Physiol. 1986 Mar;250(3 Pt 1):C442–C452. doi: 10.1152/ajpcell.1986.250.3.C442. [DOI] [PubMed] [Google Scholar]
  19. Nakahata N., Harden T. K. Regulation of inositol trisphosphate accumulation by muscarinic cholinergic and H1-histamine receptors on human astrocytoma cells. Differential induction of desensitization by agonists. Biochem J. 1987 Jan 15;241(2):337–344. doi: 10.1042/bj2410337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nakahata N., Martin M. W., Hughes A. R., Hepler J. R., Harden T. K. H1-histamine receptors on human astrocytoma cells. Mol Pharmacol. 1986 Feb;29(2):188–195. [PubMed] [Google Scholar]
  21. Orellana S. A., Solski P. A., Brown J. H. Phorbol ester inhibits phosphoinositide hydrolysis and calcium mobilization in cultured astrocytoma cells. J Biol Chem. 1985 May 10;260(9):5236–5239. [PubMed] [Google Scholar]
  22. Osugi T., Uchida S., Imaizumi T., Yoshida H. Bradykinin-induced intracellular Ca2+ elevation in neuroblastoma X glioma hybrid NG108-15 cells; relationship to the action of inositol phospholipids metabolites. Brain Res. 1986 Jul 30;379(1):84–89. doi: 10.1016/0006-8993(86)90258-1. [DOI] [PubMed] [Google Scholar]
  23. Pozzan T., Di Virgilio F., Vicentini L. M., Meldolesi J. Activation of muscarinic receptors in PC12 cells. Stimulation of Ca2+ influx and redistribution. Biochem J. 1986 Mar 15;234(3):547–553. doi: 10.1042/bj2340547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Putney J. W., Jr Muscarinic, alpha-adrenergic and peptide receptors regulate the same calcium influx sites in the parotid gland. J Physiol. 1977 Jun;268(1):139–149. doi: 10.1113/jphysiol.1977.sp011851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rasmussen H., Barrett P. Q. Calcium messenger system: an integrated view. Physiol Rev. 1984 Jul;64(3):938–984. doi: 10.1152/physrev.1984.64.3.938. [DOI] [PubMed] [Google Scholar]
  27. Siegel H., Jim K., Bolger G. T., Gengo P., Triggle D. J. Specific and non-specific desensitization of guinea-pig ileal smooth muscle. J Auton Pharmacol. 1984 Jun;4(2):109–125. doi: 10.1111/j.1474-8673.1984.tb00088.x. [DOI] [PubMed] [Google Scholar]
  28. Stolze H., Schulz I. Effect of atropine, ouabain, antimycin A, and A23187 on "trigger Ca2+ pool" in exocrine pancreas. Am J Physiol. 1980 Apr;238(4):G338–G348. doi: 10.1152/ajpgi.1980.238.4.G338. [DOI] [PubMed] [Google Scholar]
  29. Takemura H. Changes in cytosolic free calcium concentration in isolated rat parotid cells by cholinergic and beta-adrenergic agonists. Biochem Biophys Res Commun. 1985 Sep 30;131(3):1048–1055. doi: 10.1016/0006-291x(85)90196-2. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Williamson J. R., Cooper R. H., Joseph S. K., Thomas A. P. Inositol trisphosphate and diacylglycerol as intracellular second messengers in liver. Am J Physiol. 1985 Mar;248(3 Pt 1):C203–C216. doi: 10.1152/ajpcell.1985.248.3.C203. [DOI] [PubMed] [Google Scholar]
  32. Wollheim C. B., Biden T. J. Second messenger function of inositol 1,4,5-trisphosphate. Early changes in inositol phosphates, cytosolic Ca2+, and insulin release in carbamylcholine-stimulated RINm5F cells. J Biol Chem. 1986 Jun 25;261(18):8314–8319. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES