Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Sep;113(1):29–34. doi: 10.1111/j.1476-5381.1994.tb16169.x

Characterization and transduction mechanisms of purinoceptors in activated rat microglia.

J M Langosch 1, P J Gebicke-Haerter 1, W Nörenberg 1, P Illes 1
PMCID: PMC1510046  PMID: 7812623

Abstract

1. Purinoceptor agonist-induced currents in untreated (proliferating) and lipopolysaccharide- (LPS; 100 ng ml-1) treated (non-proliferating) rat microglial cells were recorded by the whole-cell patch-clamp technique. 2. In non-proliferating microglia, adenosine (0.01-100 microM), 2-methylthio ATP (3-3000 nM), ATP (0.1-1000 microM), and ATP-gamma-S (1-10 microM), but not alpha,beta-methylene ATP (alpha,beta-MeATP; 100 microM) produced a slow outward current at a holding potential of 0 mV. When K+ was replaced in the pipette solution by an equimolar concentration of Cs+ (150 mM), the 2-methylthio ATP- (300 nM) induced outward current disappeared. The effect of 2-methylthio ATP (300 nM) did not depend on the presence of extracellular Mg2+ (1 mM). The outward current response to 2-methylthio ATP (300 nM) was larger in proliferating than in non-proliferating microglia. 3. ATP (1-1000 microM) evoked a fast inward current at a holding potential of -70 mV in nonproliferating microglia, while adenosine (100-1000 microM) was inactive. When the effects of ATP were compared at 0 and -70 mV, it became evident that ATP is much more potent in evoking the outward current. 4. The 2-methylthio ATP- (300 nM) induced outward current was blocked by suramin (300 microM), but not by 8-(p-sulphophenyl)-theophylline (100 microM), while the adenosine- (1 microM) induced outward current had the reverse sensitivity to these antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
29

Selected References

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

  1. Adams D. O., Hamilton T. A. Molecular transductional mechanisms by which IFN gamma and other signals regulate macrophage development. Immunol Rev. 1987 Jun;97:5–27. doi: 10.1111/j.1600-065x.1987.tb00514.x. [DOI] [PubMed] [Google Scholar]
  2. Banati R. B., Hoppe D., Gottmann K., Kreutzberg G. W., Kettenmann H. A subpopulation of bone marrow-derived macrophage-like cells shares a unique ion channel pattern with microglia. J Neurosci Res. 1991 Dec;30(4):593–600. doi: 10.1002/jnr.490300402. [DOI] [PubMed] [Google Scholar]
  3. Bean B. P. ATP-activated channels in rat and bullfrog sensory neurons: concentration dependence and kinetics. J Neurosci. 1990 Jan;10(1):1–10. doi: 10.1523/JNEUROSCI.10-01-00001.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bean B. P. Pharmacology and electrophysiology of ATP-activated ion channels. Trends Pharmacol Sci. 1992 Mar;13(3):87–90. doi: 10.1016/0165-6147(92)90032-2. [DOI] [PubMed] [Google Scholar]
  5. Bruns R. F., Daly J. W., Snyder S. H. Adenosine receptors in brain membranes: binding of N6-cyclohexyl[3H]adenosine and 1,3-diethyl-8-[3H]phenylxanthine. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5547–5551. doi: 10.1073/pnas.77.9.5547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burnstock G., Kennedy C. Is there a basis for distinguishing two types of P2-purinoceptor? Gen Pharmacol. 1985;16(5):433–440. doi: 10.1016/0306-3623(85)90001-1. [DOI] [PubMed] [Google Scholar]
  7. Christie A., Sharma V. K., Sheu S. S. Mechanism of extracellular ATP-induced increase of cytosolic Ca2+ concentration in isolated rat ventricular myocytes. J Physiol. 1992 Jan;445:369–388. doi: 10.1113/jphysiol.1992.sp018929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dickson D. W., Mattiace L. A., Kure K., Hutchins K., Lyman W. D., Brosnan C. F. Microglia in human disease, with an emphasis on acquired immune deficiency syndrome. Lab Invest. 1991 Feb;64(2):135–156. [PubMed] [Google Scholar]
  9. Dijkstra C. D., Döpp E. A., Joling P., Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985 Mar;54(3):589–599. [PMC free article] [PubMed] [Google Scholar]
  10. Friel D. D. An ATP-sensitive conductance in single smooth muscle cells from the rat vas deferens. J Physiol. 1988 Jul;401:361–380. doi: 10.1113/jphysiol.1988.sp017167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gallin E. K. Ion channels in leukocytes. Physiol Rev. 1991 Jul;71(3):775–811. doi: 10.1152/physrev.1991.71.3.775. [DOI] [PubMed] [Google Scholar]
  12. Gebicke-Haerter P. J., Bauer J., Schobert A., Northoff H. Lipopolysaccharide-free conditions in primary astrocyte cultures allow growth and isolation of microglial cells. J Neurosci. 1989 Jan;9(1):183–194. doi: 10.1523/JNEUROSCI.09-01-00183.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  14. Illes P., Nörenberg W. Neuronal ATP receptors and their mechanism of action. Trends Pharmacol Sci. 1993 Feb;14(2):50–54. doi: 10.1016/0165-6147(93)90030-n. [DOI] [PubMed] [Google Scholar]
  15. Kennedy C. P1- and P2-purinoceptor subtypes--an update. Arch Int Pharmacodyn Ther. 1990 Jan-Feb;303:30–50. [PubMed] [Google Scholar]
  16. Kettenmann H., Banati R., Walz W. Electrophysiological behavior of microglia. Glia. 1993 Jan;7(1):93–101. doi: 10.1002/glia.440070115. [DOI] [PubMed] [Google Scholar]
  17. Kettenmann H., Hoppe D., Gottmann K., Banati R., Kreutzberg G. Cultured microglial cells have a distinct pattern of membrane channels different from peritoneal macrophages. J Neurosci Res. 1990 Jul;26(3):278–287. doi: 10.1002/jnr.490260303. [DOI] [PubMed] [Google Scholar]
  18. Nörenberg W., Appel K., Bauer J., Gebicke-Haerter P. J., Illes P. Expression of an outwardly rectifying K+ channel in rat microglia cultivated on teflon. Neurosci Lett. 1993 Sep 17;160(1):69–72. doi: 10.1016/0304-3940(93)9001-0. [DOI] [PubMed] [Google Scholar]
  19. Nörenberg W., Gebicke-Haerter P. J., Illes P. Inflammatory stimuli induce a new K+ outward current in cultured rat microglia. Neurosci Lett. 1992 Dec 7;147(2):171–174. doi: 10.1016/0304-3940(92)90587-w. [DOI] [PubMed] [Google Scholar]
  20. Nörenberg W., Gebicke-Haerter P. J., Illes P. Voltage-dependent potassium channels in activated rat microglia. J Physiol. 1994 Feb 15;475(1):15–32. doi: 10.1113/jphysiol.1994.sp020046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nörenberg W., Langosch J. M., Gebicke-Haerter P. J., Illes P. Characterization and possible function of adenosine 5'-triphosphate receptors in activated rat microglia. Br J Pharmacol. 1994 Mar;111(3):942–950. doi: 10.1111/j.1476-5381.1994.tb14830.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rieske E., Graeber M. B., Tetzlaff W., Czlonkowska A., Streit W. J., Kreutzberg G. W. Microglia and microglia-derived brain macrophages in culture: generation from axotomized rat facial nuclei, identification and characterization in vitro. Brain Res. 1989 Jul 17;492(1-2):1–14. doi: 10.1016/0006-8993(89)90883-4. [DOI] [PubMed] [Google Scholar]
  23. Streit W. J., Graeber M. B., Kreutzberg G. W. Functional plasticity of microglia: a review. Glia. 1988;1(5):301–307. doi: 10.1002/glia.440010502. [DOI] [PubMed] [Google Scholar]
  24. Thomas W. E. Brain macrophages: evaluation of microglia and their functions. Brain Res Brain Res Rev. 1992 Jan-Apr;17(1):61–74. doi: 10.1016/0165-0173(92)90007-9. [DOI] [PubMed] [Google Scholar]
  25. Walz W., Ilschner S., Ohlemeyer C., Banati R., Kettenmann H. Extracellular ATP activates a cation conductance and a K+ conductance in cultured microglial cells from mouse brain. J Neurosci. 1993 Oct;13(10):4403–4411. doi: 10.1523/JNEUROSCI.13-10-04403.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES