Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1997 May 15;501(Pt 1):67–75. doi: 10.1111/j.1469-7793.1997.067bo.x

Modulation by adenosine of GABA-activated current in rat dorsal root ganglion neurons.

H Z Hu 1, Z W Li 1
PMCID: PMC1159505  PMID: 9174995

Abstract

1. The modulation by adenosine of GABA-activated current (IGADA) was studied in freshly isolated rat dorsal root ganglion (DRG) neurons using the whole-cell patch-clamp technique. 2. In most of the DRG neurons examined (68/90, 75.5%) adenosine (1-10 microM) suppressed IGABA, while in some neurons examined, it potentiated (16/90, 17.8%) IGABA. It exerted no effects on IGABA in a few cells (6/90, 6.7%). 3. Adenosine shifted the GABA concentration-response curve downward with no significant change of the EC50. The maximal response to GABA was suppressed by 29.6 +/- 2.6%. The adenosine-induced inhibition of IGABA showed no voltage dependence. 4. 8-Cyclopentyl-1,3-dimethylxanthine (DPCPX; 1 microM), a selective A1 adenosine receptor antagonist, partially reversed adenosine inhibition of IGABA and completely blocked N6-cyclo-hexyladenosine (CHA; an A1 adenosine receptor agonist) inhibition of IGABA. DPCPX (1 microM) also blocked the suppression of IGABA by 2-chloroadenosine (CADO). CGS21680, a selective A2A adenosine receptor agonist, did not inhibit IGABA and DMPX, a selective A2A adenosine receptor antagonist, did not prevent adenosine inhibition of IGABA. 5. Intracellular application of H-7 (20 microM; a protein kinase C inhibitor) reversed adenosine inhibition of IGABA while inclusion of cAMP (1 mM), H-9 (20 microM; a protein kinase A inhibitor) and BAPTA (10 mM; a chelator of calcium ions) in the recording pipette did not affect the depression of IGABA by adenosine. IGABA was also suppressed by internal perfusion of PMA, a protein kinase C activator. 6. The results suggest that adenosine, as a neuromodulator, exerts a modulatory effect on the GABA-induced presynaptic inhibition in primary sensory transmission.

Full text

PDF
67

Selected References

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

  1. Akhondzadeh S., Stone T. W. Interaction between adenosine and GABAA receptors on hippocampal neurones. Brain Res. 1994 Dec 5;665(2):229–236. doi: 10.1016/0006-8993(94)91342-0. [DOI] [PubMed] [Google Scholar]
  2. Burnstock G. Overview. Purinergic mechanisms. Ann N Y Acad Sci. 1990;603:1–18. doi: 10.1111/j.1749-6632.1990.tb37657.x. [DOI] [PubMed] [Google Scholar]
  3. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  4. Christofi F. L., McDonald T. J., Cook M. A. Adenosine receptors are coupled negatively to release of tachykinin(s) from enteric nerve endings. J Pharmacol Exp Ther. 1990 Apr;253(1):290–295. [PubMed] [Google Scholar]
  5. DeLander G. E., Wahl J. J. Behavior induced by putative nociceptive neurotransmitters is inhibited by adenosine or adenosine analogs coadministered intrathecally. J Pharmacol Exp Ther. 1988 Aug;246(2):565–570. [PubMed] [Google Scholar]
  6. Doi T., Kuzuna S., Maki Y. Spinal antinociceptive effects of adenosine compounds in mice. Eur J Pharmacol. 1987 Jun 4;137(2-3):227–231. doi: 10.1016/0014-2999(87)90226-3. [DOI] [PubMed] [Google Scholar]
  7. Dolphin A. C., Prestwich S. A. Pertussis toxin reverses adenosine inhibition of neuronal glutamate release. Nature. 1985 Jul 11;316(6024):148–150. doi: 10.1038/316148a0. [DOI] [PubMed] [Google Scholar]
  8. Désarmenien M., Feltz P., Occhipinti G., Santangelo F., Schlichter R. Coexistence of GABAA and GABAB receptors on A delta and C primary afferents. Br J Pharmacol. 1984 Feb;81(2):327–333. doi: 10.1111/j.1476-5381.1984.tb10082.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fredholm B. B., Abbracchio M. P., Burnstock G., Daly J. W., Harden T. K., Jacobson K. A., Leff P., Williams M. Nomenclature and classification of purinoceptors. Pharmacol Rev. 1994 Jun;46(2):143–156. [PMC free article] [PubMed] [Google Scholar]
  10. Hidaka H., Inagaki M., Kawamoto S., Sasaki Y. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984 Oct 9;23(21):5036–5041. doi: 10.1021/bi00316a032. [DOI] [PubMed] [Google Scholar]
  11. Jahr C. E., Jessell T. M. ATP excites a subpopulation of rat dorsal horn neurones. Nature. 1983 Aug 25;304(5928):730–733. doi: 10.1038/304730a0. [DOI] [PubMed] [Google Scholar]
  12. Kardos J., Kovacs I. Binding interaction of gamma aminobutyric acid A and B receptors in cell culture. Neuroreport. 1991 Sep;2(9):541–543. doi: 10.1097/00001756-199109000-00011. [DOI] [PubMed] [Google Scholar]
  13. Klishin A., Lozovaya N., Krishtal O. A1 adenosine receptors differentially regulate the N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor-mediated components of hippocampal excitatory postsynaptic current in a Ca2+/Mg(2+)-dependent manner. Neuroscience. 1995 Apr;65(4):947–953. doi: 10.1016/0306-4522(94)00518-a. [DOI] [PubMed] [Google Scholar]
  14. Krishtal O. A., Marchenko S. M., Pidoplichko V. I. Receptor for ATP in the membrane of mammalian sensory neurones. Neurosci Lett. 1983 Jan 31;35(1):41–45. doi: 10.1016/0304-3940(83)90524-4. [DOI] [PubMed] [Google Scholar]
  15. Li C., Peoples R. W., Li Z., Weight F. F. Zn2+ potentiates excitatory action of ATP on mammalian neurons. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8264–8267. doi: 10.1073/pnas.90.17.8264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lin Z. W., Li Z. W. [Responses mediated by GABAA and GABAB receptors on the somatic membrane of toad dorsal root ganglion neurones]. Sheng Li Xue Bao. 1993 Apr;45(2):117–123. [PubMed] [Google Scholar]
  17. MacDonald R. L., Skerritt J. H., Werz M. A. Adenosine agonists reduce voltage-dependent calcium conductance of mouse sensory neurones in cell culture. J Physiol. 1986 Jan;370:75–90. doi: 10.1113/jphysiol.1986.sp015923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mayfield R. D., Suzuki F., Zahniser N. R. Adenosine A2a receptor modulation of electrically evoked endogenous GABA release from slices of rat globus pallidus. J Neurochem. 1993 Jun;60(6):2334–2337. doi: 10.1111/j.1471-4159.1993.tb03526.x. [DOI] [PubMed] [Google Scholar]
  19. Nagy J. I., Buss M., LaBella L. A., Daddona P. E. Immunohistochemical localization of adenosine deaminase in primary afferent neurons of the rat. Neurosci Lett. 1984 Jul 27;48(2):133–138. doi: 10.1016/0304-3940(84)90008-9. [DOI] [PubMed] [Google Scholar]
  20. Otsuka M., Yanagisawa M. Pain and neurotransmitters. Cell Mol Neurobiol. 1990 Sep;10(3):293–302. doi: 10.1007/BF00711176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Petcoff D. W., Cooper D. M. Adenosine receptor agonists inhibit inositol phosphate accumulation in rat striatal slices. Eur J Pharmacol. 1987 Jun 4;137(2-3):269–271. doi: 10.1016/0014-2999(87)90234-2. [DOI] [PubMed] [Google Scholar]
  22. Raymond L. A., Blackstone C. D., Huganir R. L. Phosphorylation of amino acid neurotransmitter receptors in synaptic plasticity. Trends Neurosci. 1993 Apr;16(4):147–153. doi: 10.1016/0166-2236(93)90123-4. [DOI] [PubMed] [Google Scholar]
  23. Redman R. S., Silinsky E. M. A selective adenosine antagonist (8-cyclopentyl-1,3-dipropylxanthine) eliminates both neuromuscular depression and the action of exogenous adenosine by an effect on A1 receptors. Mol Pharmacol. 1993 Oct;44(4):835–840. [PubMed] [Google Scholar]
  24. Sawynok J., Reid A., Isbrucker R. Adenosine mediates calcium-induced antinociception and potentiation of noradrenergic antinociception in the spinal cord. Brain Res. 1990 Aug 6;524(2):187–195. doi: 10.1016/0006-8993(90)90689-9. [DOI] [PubMed] [Google Scholar]
  25. Sebastião A. M., Ribeiro J. A. Adenosine A2 receptor-mediated excitatory actions on the nervous system. Prog Neurobiol. 1996 Feb;48(3):167–189. doi: 10.1016/0301-0082(95)00035-6. [DOI] [PubMed] [Google Scholar]
  26. Sebastião A. M., Ribeiro J. A. Interactions between adenosine and phorbol esters or lithium at the frog neuromuscular junction. Br J Pharmacol. 1990 May;100(1):55–62. doi: 10.1111/j.1476-5381.1990.tb12051.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Williams M. Purine nucleosides and nucleotides as central nervous system modulators. Adenosine as the prototypic paracrine neuroactive substance. Ann N Y Acad Sci. 1990;603:93–107. doi: 10.1111/j.1749-6632.1990.tb37664.x. [DOI] [PubMed] [Google Scholar]
  28. Yamada K., Akasu T. Substance P suppresses GABAA receptor function via protein kinase C in primary sensory neurones of bullfrogs. J Physiol. 1996 Oct 15;496(Pt 2):439–449. doi: 10.1113/jphysiol.1996.sp021697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yoon K. W., Rothman S. M. Adenosine inhibits excitatory but not inhibitory synaptic transmission in the hippocampus. J Neurosci. 1991 May;11(5):1375–1380. doi: 10.1523/JNEUROSCI.11-05-01375.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Zhou X. P., Wu X. P., Guan B. C., Li Z. W. Modulatory effects of gonadorelin on GABA-induced depolarization and GABA-activated current in rat spinal ganglion neurons. Zhongguo Yao Li Xue Bao. 1996 Jan;17(1):31–34. [PubMed] [Google Scholar]
  31. Zhu X., Zhu H., Bao Y. D. [Glutamate receptor and GABA receptor expressed in amphibian oocytes after injection of chicken retina mRNA]. Sheng Li Xue Bao. 1994 Oct;46(5):417–426. [PubMed] [Google Scholar]
  32. de Mendonça A., Sebastião A. M., Ribeiro J. A. Inhibition of NMDA receptor-mediated currents in isolated rat hippocampal neurones by adenosine A1 receptor activation. Neuroreport. 1995 May 30;6(8):1097–1100. doi: 10.1097/00001756-199505300-00006. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES