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. 1995 Jul;115(5):801–810. doi: 10.1111/j.1476-5381.1995.tb15004.x

Adenosine A1 receptor-mediated changes in basal and histamine-stimulated levels of intracellular calcium in primary rat astrocytes.

M C Peakman 1, S J Hill 1
PMCID: PMC1908518  PMID: 8548180

Abstract

1. The effects of adenosine A1 receptor stimulation on basal and histamine-stimulated levels of intracellular free calcium ion concentration ([Ca2+]i) have been investigated in primary astrocyte cultures derived from neonatal rat forebrains. 2. Histamine (0.1 microM-1 mM) caused rapid, concentration-dependent increases in [Ca2+]i over basal levels in single type-2 astrocytes in the presence of extracellular calcium. A maximum mean increase of 1,468 +/- 94 nM over basal levels was recorded in 90% of type-2 cells treated with 1 mM histamine (n = 49). The percentage of type-2 cells exhibiting calcium increases in response to histamine appeared to vary in a concentration-dependent manner. However, the application of 1 mM histamine to type-1 astrocytes had less effect, eliciting a mean increase in [Ca2+]i of 805 +/- 197 nM over basal levels in only 30% of the cells observed (n = 24). 3. In the presence of extracellular calcium, the A1 receptor-selective agonist, N6-cyclopentyladenosine (CPA, 10 microM), caused a maximum mean increase in [Ca2+]i of 1,110 +/- 181 nM over basal levels in 30% of type-2 astrocytes observed (n = 53). The size of this response was concentration-dependent; however, the percentage of type-2 cells exhibiting calcium increases in response to CPA did not appear to vary in a concentration-dependent manner. A mean calcium increase of 605 +/- 89 nM over basal levels was also recorded in 23% of type-1 astrocytes treated with 10 microM CPA (n = 30). 4. In the absence of extracellular calcium, in medium containing 0.1 mM EGTA, a mean increase in [Ca2+]i of 504 +/- 67 nM over basal levels was recorded in 41% of type-2 astrocytes observed (n = 41) after stimulation with 1 microM CPA. However, in the presence of extracellular calcium, pretreatment with the A1 receptor-selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine, for 5-10 min before stimulation with 1 microM CPA, completely antagonized the response in 100% of the cells observed. 5. In type-2 astrocytes, prestimulation with 10 nM CPA significantly increased the size of the calcium response produced by 0.1 microM histamine and the percentage of responding cells. Treatment with 0.1 microM histamine alone caused a mean calcium increase of 268 +/- 34 nM in 41% of the cells observed (n = 34). After treatment with 10 nM CPA, mean calcium increase of 543 +/- 97 nM was recorded in 100% of the cells observed (n = 33).(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Arend L. J., Burnatowska-Hledin M. A., Spielman W. S. Adenosine receptor-mediated calcium mobilization in cortical collecting tubule cells. Am J Physiol. 1988 Nov;255(5 Pt 1):C581–C588. doi: 10.1152/ajpcell.1988.255.5.C581. [DOI] [PubMed] [Google Scholar]
  2. Arend L. J., Handler J. S., Rhim J. S., Gusovsky F., Spielman W. S. Adenosine-sensitive phosphoinositide turnover in a newly established renal cell line. Am J Physiol. 1989 Jun;256(6 Pt 2):F1067–F1074. doi: 10.1152/ajprenal.1989.256.6.F1067. [DOI] [PubMed] [Google Scholar]
  3. Brown E., Kendall D. A., Nahorski S. R. Inositol phospholipid hydrolysis in rat cerebral cortical slices: I. Receptor characterisation. J Neurochem. 1984 May;42(5):1379–1387. doi: 10.1111/j.1471-4159.1984.tb02798.x. [DOI] [PubMed] [Google Scholar]
  4. Bruns R. F., Fergus J. H., Badger E. W., Bristol J. A., Santay L. A., Hays S. J. PD 115,199: an antagonist ligand for adenosine A2 receptors. Naunyn Schmiedebergs Arch Pharmacol. 1987 Jan;335(1):64–69. doi: 10.1007/BF00165038. [DOI] [PubMed] [Google Scholar]
  5. Clapham D. E., Neer E. J. New roles for G-protein beta gamma-dimers in transmembrane signalling. Nature. 1993 Sep 30;365(6445):403–406. doi: 10.1038/365403a0. [DOI] [PubMed] [Google Scholar]
  6. Daly J. W., Butts-Lamb P., Padgett W. Subclasses of adenosine receptors in the central nervous system: interaction with caffeine and related methylxanthines. Cell Mol Neurobiol. 1983 Mar;3(1):69–80. doi: 10.1007/BF00734999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dave V., Gordon G. W., McCarthy K. D. Cerebral type 2 astroglia are heterogeneous with respect to their ability to respond to neuroligands linked to calcium mobilization. Glia. 1991;4(5):440–447. doi: 10.1002/glia.440040503. [DOI] [PubMed] [Google Scholar]
  8. Dickenson J. M., Hill S. J. Adenosine A1-receptor stimulated increases in intracellular calcium in the smooth muscle cell line, DDT1MF-2. Br J Pharmacol. 1993 Jan;108(1):85–92. doi: 10.1111/j.1476-5381.1993.tb13444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dickenson J. M., Hill S. J. Histamine H1-receptor-mediated calcium influx in DDT1MF-2 cells. Biochem J. 1992 Jun 1;284(Pt 2):425–431. doi: 10.1042/bj2840425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dickenson J. M., Hill S. J. Histamine-stimulated increases in intracellular calcium in the smooth muscle cell line, DDT1MF-2. Biochem Pharmacol. 1991 Sep 27;42(8):1545–1550. doi: 10.1016/0006-2952(91)90423-3. [DOI] [PubMed] [Google Scholar]
  11. Dickenson J. M., Hill S. J. Interactions between adenosine A1- and histamine H1-receptors. Int J Biochem. 1994 Aug;26(8):959–969. doi: 10.1016/0020-711x(94)90066-3. [DOI] [PubMed] [Google Scholar]
  12. Dickenson J. M., Hill S. J. Intracellular cross-talk between receptors coupled to phospholipase C via pertussis toxin-sensitive and insensitive G-proteins in DDT1MF-2 cells. Br J Pharmacol. 1993 Jul;109(3):719–724. doi: 10.1111/j.1476-5381.1993.tb13633.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ebersolt C., Premont J., Prochiantz A., Perez M., Bockaert J. Inhibition of brain adenylate cyclase by A1 adenosine receptors: pharmacological characteristics and locations. Brain Res. 1983 May 9;267(1):123–129. doi: 10.1016/0006-8993(83)91045-4. [DOI] [PubMed] [Google Scholar]
  14. Fukui H., Inagaki N., Ito S., Kubo A., Kondoh H., Yamatodani A., Wada H. Histamine H1-receptors on astrocytes in primary cultures: a possible target for histaminergic neurones. Agents Actions Suppl. 1991;33:161–180. doi: 10.1007/978-3-0348-7309-3_12. [DOI] [PubMed] [Google Scholar]
  15. Furlong T. J., Pierce K. D., Selbie L. A., Shine J. Molecular characterization of a human brain adenosine A2 receptor. Brain Res Mol Brain Res. 1992 Sep;15(1-2):62–66. doi: 10.1016/0169-328x(92)90152-2. [DOI] [PubMed] [Google Scholar]
  16. Galietta L. J., Rasola A., Rugolo M., Zottini M., Mastrocola T., Gruenert D. C., Romeo G. Extracellular 2-chloroadenosine and ATP stimulate volume-sensitive Cl- current and calcium mobilization in human tracheal 9HTEo- cells. FEBS Lett. 1992 Jun 8;304(1):61–65. doi: 10.1016/0014-5793(92)80589-9. [DOI] [PubMed] [Google Scholar]
  17. Gerwins P., Fredholm B. B. ATP and its metabolite adenosine act synergistically to mobilize intracellular calcium via the formation of inositol 1,4,5-trisphosphate in a smooth muscle cell line. J Biol Chem. 1992 Aug 15;267(23):16081–16087. [PubMed] [Google Scholar]
  18. Gerwins P., Fredholm B. B. Stimulation of adenosine A1 receptors and bradykinin receptors, which act via different G proteins, synergistically raises inositol 1,4,5-trisphosphate and intracellular free calcium in DDT1 MF-2 smooth muscle cells. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7330–7334. doi: 10.1073/pnas.89.16.7330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Hollingsworth E. B., De la Cruz R. A., Daly J. W. Accumulations of inositol phosphates and cyclic AMP in brain slices: synergistic interactions of histamine and 2-chloroadenosine. Eur J Pharmacol. 1986 Mar 11;122(1):45–50. doi: 10.1016/0014-2999(86)90156-1. [DOI] [PubMed] [Google Scholar]
  21. Inagaki N., Fukui H., Ito S., Wada H. Type-2 astrocytes show intracellular Ca2+ elevation in response to various neuroactive substances. Neurosci Lett. 1991 Jul 22;128(2):257–260. doi: 10.1016/0304-3940(91)90274-w. [DOI] [PubMed] [Google Scholar]
  22. Inagaki N., Fukui H., Ito S., Yamatodani A., Wada H. Single type-2 astrocytes show multiple independent sites of Ca2+ signaling in response to histamine. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4215–4219. doi: 10.1073/pnas.88.10.4215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Iredale P. A., Alexander S. P., Hill S. J. Coupling of a transfected human brain A1 adenosine receptor in CHO-K1 cells to calcium mobilisation via a pertussis toxin-sensitive mechanism. Br J Pharmacol. 1994 Apr;111(4):1252–1256. doi: 10.1111/j.1476-5381.1994.tb14880.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jarvis M. F., Schulz R., Hutchison A. J., Do U. H., Sills M. A., Williams M. [3H]CGS 21680, a selective A2 adenosine receptor agonist directly labels A2 receptors in rat brain. J Pharmacol Exp Ther. 1989 Dec;251(3):888–893. [PubMed] [Google Scholar]
  25. Jensen A. M., Chiu S. Y. Differential intracellular calcium responses to glutamate in type 1 and type 2 cultured brain astrocytes. J Neurosci. 1991 Jun;11(6):1674–1684. doi: 10.1523/JNEUROSCI.11-06-01674.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kastritsis C. H., Salm A. K., McCarthy K. Stimulation of the P2Y purinergic receptor on type 1 astroglia results in inositol phosphate formation and calcium mobilization. J Neurochem. 1992 Apr;58(4):1277–1284. doi: 10.1111/j.1471-4159.1992.tb11339.x. [DOI] [PubMed] [Google Scholar]
  27. Kondou H., Inagaki N., Fukui H., Koyama Y., Kanamura A., Wada H. Histamine-induced inositol phosphate accumulation in type-2 astrocytes. Biochem Biophys Res Commun. 1991 Jun 14;177(2):734–738. doi: 10.1016/0006-291x(91)91849-8. [DOI] [PubMed] [Google Scholar]
  28. Kriegler S., Chiu S. Y. Calcium signaling of glial cells along mammalian axons. J Neurosci. 1993 Oct;13(10):4229–4245. doi: 10.1523/JNEUROSCI.13-10-04229.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lerea L. S., McCarthy K. D. Astroglial cells in vitro are heterogeneous with respect to expression of the alpha 1-adrenergic receptor. Glia. 1989;2(3):135–147. doi: 10.1002/glia.440020302. [DOI] [PubMed] [Google Scholar]
  30. Libert F., Schiffmann S. N., Lefort A., Parmentier M., Gérard C., Dumont J. E., Vanderhaeghen J. J., Vassart G. The orphan receptor cDNA RDC7 encodes an A1 adenosine receptor. EMBO J. 1991 Jul;10(7):1677–1682. doi: 10.1002/j.1460-2075.1991.tb07691.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Libert F., Van Sande J., Lefort A., Czernilofsky A., Dumont J. E., Vassart G., Ensinger H. A., Mendla K. D. Cloning and functional characterization of a human A1 adenosine receptor. Biochem Biophys Res Commun. 1992 Sep 16;187(2):919–926. doi: 10.1016/0006-291x(92)91285-x. [DOI] [PubMed] [Google Scholar]
  32. Linden J., Taylor H. E., Robeva A. S., Tucker A. L., Stehle J. H., Rivkees S. A., Fink J. S., Reppert S. M. Molecular cloning and functional expression of a sheep A3 adenosine receptor with widespread tissue distribution. Mol Pharmacol. 1993 Sep;44(3):524–532. [PubMed] [Google Scholar]
  33. Maenhaut C., Van Sande J., Libert F., Abramowicz M., Parmentier M., Vanderhaegen J. J., Dumont J. E., Vassart G., Schiffmann S. RDC8 codes for an adenosine A2 receptor with physiological constitutive activity. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1169–1178. doi: 10.1016/s0006-291x(05)80909-x. [DOI] [PubMed] [Google Scholar]
  34. Marin P., Tencé M., Delumeau J. C., Glowinski J., Prémont J. Adenosine and somatostatin potentiate the alpha 1-adrenergic activation of phospholipase C in striatal astrocytes through a mechanism involving arachidonic acid and glutamate. Biochem Soc Trans. 1993 Nov;21(4):1114–1119. doi: 10.1042/bst0211114. [DOI] [PubMed] [Google Scholar]
  35. Marsh K. A., Hill S. J. Characteristics of the bradykinin-induced changes in intracellular calcium ion concentration of single bovine tracheal smooth muscle cells. Br J Pharmacol. 1993 Sep;110(1):29–35. doi: 10.1111/j.1476-5381.1993.tb13767.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. McCarthy K. D., Salm A. K. Pharmacologically-distinct subsets of astroglia can be identified by their calcium response to neuroligands. Neuroscience. 1991;41(2-3):325–333. doi: 10.1016/0306-4522(91)90330-q. [DOI] [PubMed] [Google Scholar]
  37. Neylon C. B., Hoyland J., Mason W. T., Irvine R. F. Spatial dynamics of intracellular calcium in agonist-stimulated vascular smooth muscle cells. Am J Physiol. 1990 Oct;259(4 Pt 1):C675–C686. doi: 10.1152/ajpcell.1990.259.4.C675. [DOI] [PubMed] [Google Scholar]
  38. Nilsson M., Hansson E., Rönnbäck L. Adrenergic and 5-HT2 receptors on the same astroglial cell. A microspectrofluorimetric study on cytosolic Ca2+ responses in single cells in primary culture. Brain Res Dev Brain Res. 1991 Nov 19;63(1-2):33–41. doi: 10.1016/0165-3806(91)90064-p. [DOI] [PubMed] [Google Scholar]
  39. Nilsson M., Hansson E., Rönnbäck L. Heterogeneity among astroglial cells with respect to 5HT-evoked cytosolic Ca2+ responses. A microspectrofluorimetric study on single cells in primary culture. Life Sci. 1991;49(18):1339–1350. doi: 10.1016/0024-3205(91)90198-k. [DOI] [PubMed] [Google Scholar]
  40. Ogata T., Nakamura Y., Tsuji K., Shibata T., Kataoka K., Schubert P. Adenosine enhances intracellular Ca2+ mobilization in conjunction with metabotropic glutamate receptor activation by t-ACPD in cultured hippocampal astrocytes. Neurosci Lett. 1994 Mar 28;170(1):5–8. doi: 10.1016/0304-3940(94)90225-9. [DOI] [PubMed] [Google Scholar]
  41. Olah M. E., Ren H., Ostrowski J., Jacobson K. A., Stiles G. L. Cloning, expression, and characterization of the unique bovine A1 adenosine receptor. Studies on the ligand binding site by site-directed mutagenesis. J Biol Chem. 1992 May 25;267(15):10764–10770. [PMC free article] [PubMed] [Google Scholar]
  42. Olivera A., López-Rivas A., López-Novoa J. M. Adenosine stimulates Ca2+ fluxes and increases cytosolic free Ca2+ in cultured rat mesangial cells. Biochem J. 1992 Mar 15;282(Pt 3):871–876. doi: 10.1042/bj2820871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Peakman M. C., Hill S. J. Adenosine A2B-receptor-mediated cyclic AMP accumulation in primary rat astrocytes. Br J Pharmacol. 1994 Jan;111(1):191–198. doi: 10.1111/j.1476-5381.1994.tb14043.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Pierce K. D., Furlong T. J., Selbie L. A., Shine J. Molecular cloning and expression of an adenosine A2b receptor from human brain. Biochem Biophys Res Commun. 1992 Aug 31;187(1):86–93. doi: 10.1016/s0006-291x(05)81462-7. [DOI] [PubMed] [Google Scholar]
  45. Rivkees S. A., Reppert S. M. RFL9 encodes an A2b-adenosine receptor. Mol Endocrinol. 1992 Oct;6(10):1598–1604. doi: 10.1210/mend.6.10.1333049. [DOI] [PubMed] [Google Scholar]
  46. Salvatore C. A., Jacobson M. A., Taylor H. E., Linden J., Johnson R. G. Molecular cloning and characterization of the human A3 adenosine receptor. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10365–10369. doi: 10.1073/pnas.90.21.10365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Schiemann W. P., Doggwiler K. O., Buxton I. L. Action of adenosine in estrogen-primed nonpregnant guinea pig myometrium: characterization of the smooth muscle receptor and coupling to phosphoinositide metabolism. J Pharmacol Exp Ther. 1991 Aug;258(2):429–437. [PubMed] [Google Scholar]
  48. Weinberg J. M., Davis J. A., Shayman J. A., Knight P. R. Alterations of cytosolic calcium in LLC-PK1 cells induced by vasopressin and exogenous purines. Am J Physiol. 1989 May;256(5 Pt 1):C967–C976. doi: 10.1152/ajpcell.1989.256.5.C967. [DOI] [PubMed] [Google Scholar]
  49. White T. E., Dickenson J. M., Alexander S. P., Hill S. J. Adenosine A1-receptor stimulation of inositol phospholipid hydrolysis and calcium mobilisation in DDT1 MF-2 cells. Br J Pharmacol. 1992 May;106(1):215–221. doi: 10.1111/j.1476-5381.1992.tb14317.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. White T. E., Dickenson J. M., Hill S. J. Histamine H1-receptor-mediated inositol phospholipid hydrolysis in DDT1MF-2 cells: agonist and antagonist properties. Br J Pharmacol. 1993 Jan;108(1):196–203. doi: 10.1111/j.1476-5381.1993.tb13462.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Yakel J. L., Warren R. A., Reppert S. M., North R. A. Functional expression of adenosine A2b receptor in Xenopus oocytes. Mol Pharmacol. 1993 Feb;43(2):277–280. [PubMed] [Google Scholar]
  52. Zhou Q. Y., Li C., Olah M. E., Johnson R. A., Stiles G. L., Civelli O. Molecular cloning and characterization of an adenosine receptor: the A3 adenosine receptor. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7432–7436. doi: 10.1073/pnas.89.16.7432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. el-Etr M., Lombes M., Baulieu E. E., Erlanger B. F. A monoclonal anti-idiotypic 'internal image' antibody that recognizes the A1 adenosine receptor potentiates the alpha 1-adrenergic activation of phospholipase C in primary cultures of mouse striatal astrocytes. Neurosci Lett. 1992 Sep 28;145(1):15–18. doi: 10.1016/0304-3940(92)90192-a. [DOI] [PubMed] [Google Scholar]
  54. el-Etr M., Marin P., Tence M., Delumeau J. C., Cordier J., Glowinski J., Premont J. 2-Chloroadenosine potentiates the alpha 1-adrenergic activation of phospholipase C through a mechanism involving arachidonic acid and glutamate in striatal astrocytes. J Neurosci. 1992 Apr;12(4):1363–1369. doi: 10.1523/JNEUROSCI.12-04-01363.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. van Calker D., Müller M., Hamprecht B. Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem. 1979 Nov;33(5):999–1005. doi: 10.1111/j.1471-4159.1979.tb05236.x. [DOI] [PubMed] [Google Scholar]

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