Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Aug;118(8):2115–2125. doi: 10.1111/j.1476-5381.1996.tb15651.x

Potentiation of chloride responses to glycine by three 5-HT3 antagonists in rat spinal neurones.

D Chesnoy-Marchais 1
PMCID: PMC1909912  PMID: 8864550

Abstract

1. Modulations of Cl- responses to glycine by 5-hydroxytryptamine ligands were studied in cultured spinal neurones, by the whole-cell recording technique. 2. Three 5-HT3 antagonists were found to potentiate reversibly responses to low concentrations of glycine. Potentiations were induced by micromolar concentrations of LY-278,584 (1-10 microM) and by concentrations of MDL-72222 or ICS-205,930 between 10 nM and 1 microM. 3. Potentiations were observed over the whole voltage range without any change in the reversal potential of the glycine responses and without affecting the resting conductance. 4. The degree of potentiation was variable among cells. It increased with the concentration of the modulator, but only up to 100 nM for MDL-72222 and ICS-205,930. 5. The potentiation appeared to result from an increase in the affinity for glycine of glycine receptors. 6. Neither the blockade of glycine uptake by Na+ removal, nor the excision of membrane patches prevented the potentiation. 7. At high concentrations (10 microM), both MDL-72222 and ICS-205,930 had, in contrast, a blocking effect on glycine responses. 8. Potentiation by LY-278,584 and a dose-dependent modulation by MDL-72222 were also observed for taurine responses. 9. The effects on glycine responses of various ligands of 5-HT3 receptors (including agonists) are discussed. The ability of LY-278,584, MDL-72222 and ICS-205,930 to potentiate glycine responses appears to be independent of their known 5-HT3 receptor antagonist properties. It would be interesting to look for chemically related drugs that would be specific potentiators of glycine responses.

Full text

PDF
2115

Selected References

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

  1. Bloomenthal A. B., Goldwater E., Pritchett D. B., Harrison N. L. Biphasic modulation of the strychnine-sensitive glycine receptor by Zn2+. Mol Pharmacol. 1994 Dec;46(6):1156–1159. [PubMed] [Google Scholar]
  2. Boess F. G., Sepúlveda M. I., Lummis S. C., Martin I. L. 5-HT3 receptors in NG108-15 neuroblastoma x glioma cells: effect of the novel agonist 1-(m-chlorophenyl)-biguanide. Neuropharmacology. 1992 Jun;31(6):561–564. doi: 10.1016/0028-3908(92)90188-u. [DOI] [PubMed] [Google Scholar]
  3. Chesnoy-Marchais D., Barthe J. Y. Voltage-dependent block of NMDA responses by 5-HT agonists in ventral spinal cord neurones. Br J Pharmacol. 1996 Jan;117(1):133–141. doi: 10.1111/j.1476-5381.1996.tb15165.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Guastella J., Brecha N., Weigmann C., Lester H. A., Davidson N. Cloning, expression, and localization of a rat brain high-affinity glycine transporter. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7189–7193. doi: 10.1073/pnas.89.15.7189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hales T. G., Lambert J. J. Modulation of GABAA and glycine receptors by chlormethiazole. Eur J Pharmacol. 1992 Jan 21;210(3):239–246. doi: 10.1016/0014-2999(92)90410-6. [DOI] [PubMed] [Google Scholar]
  6. Hales T. G., Lambert J. J. The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones. Br J Pharmacol. 1991 Nov;104(3):619–628. doi: 10.1111/j.1476-5381.1991.tb12479.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hoyer D., Clarke D. E., Fozard J. R., Hartig P. R., Martin G. R., Mylecharane E. J., Saxena P. R., Humphrey P. P. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev. 1994 Jun;46(2):157–203. [PubMed] [Google Scholar]
  8. Jones M. V., Brooks P. A., Harrison N. L. Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics. J Physiol. 1992 Apr;449:279–293. doi: 10.1113/jphysiol.1992.sp019086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Klein R. L., Sanna E., McQuilkin S. J., Whiting P. J., Harris R. A. Effects of 5-HT3 receptor antagonists on binding and function of mouse and human GABAA receptors. Eur J Pharmacol. 1994 Jul 15;268(2):237–246. doi: 10.1016/0922-4106(94)90194-5. [DOI] [PubMed] [Google Scholar]
  10. Kuhse J., Betz H., Kirsch J. The inhibitory glycine receptor: architecture, synaptic localization and molecular pathology of a postsynaptic ion-channel complex. Curr Opin Neurobiol. 1995 Jun;5(3):318–323. doi: 10.1016/0959-4388(95)80044-1. [DOI] [PubMed] [Google Scholar]
  11. Lambert J. J., Belelli D., Hill-Venning C., Peters J. A. Neurosteroids and GABAA receptor function. Trends Pharmacol Sci. 1995 Sep;16(9):295–303. doi: 10.1016/s0165-6147(00)89058-6. [DOI] [PubMed] [Google Scholar]
  12. Lambert J. J., Peters J. A., Hales T. G., Dempster J. The properties of 5-HT3 receptors in clonal cell lines studied by patch-clamp techniques. Br J Pharmacol. 1989 May;97(1):27–40. doi: 10.1111/j.1476-5381.1989.tb11920.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Langosch D., Laube B., Rundström N., Schmieden V., Bormann J., Betz H. Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia. EMBO J. 1994 Sep 15;13(18):4223–4228. doi: 10.1002/j.1460-2075.1994.tb06742.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Laube B., Kuhse J., Rundström N., Kirsch J., Schmieden V., Betz H. Modulation by zinc ions of native rat and recombinant human inhibitory glycine receptors. J Physiol. 1995 Mar 15;483(Pt 3):613–619. doi: 10.1113/jphysiol.1995.sp020610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lewis C. A., Ahmed Z., Faber D. S. A characterization of glycinergic receptors present in cultured rat medullary neurons. J Neurophysiol. 1991 Oct;66(4):1291–1303. doi: 10.1152/jn.1991.66.4.1291. [DOI] [PubMed] [Google Scholar]
  16. Liu Q. R., López-Corcuera B., Mandiyan S., Nelson H., Nelson N. Cloning and expression of a spinal cord- and brain-specific glycine transporter with novel structural features. J Biol Chem. 1993 Oct 25;268(30):22802–22808. [PubMed] [Google Scholar]
  17. Lynch J. W., Rajendra S., Barry P. H., Schofield P. R. Mutations affecting the glycine receptor agonist transduction mechanism convert the competitive antagonist, picrotoxin, into an allosteric potentiator. J Biol Chem. 1995 Jun 9;270(23):13799–13806. doi: 10.1074/jbc.270.23.13799. [DOI] [PubMed] [Google Scholar]
  18. Macdonald R. L., Olsen R. W. GABAA receptor channels. Annu Rev Neurosci. 1994;17:569–602. doi: 10.1146/annurev.ne.17.030194.003033. [DOI] [PubMed] [Google Scholar]
  19. Maricq A. V., Peterson A. S., Brake A. J., Myers R. M., Julius D. Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science. 1991 Oct 18;254(5030):432–437. doi: 10.1126/science.1718042. [DOI] [PubMed] [Google Scholar]
  20. Neijt H. C., te Duits I. J., Vijverberg H. P. Pharmacological characterization of serotonin 5-HT3 receptor-mediated electrical response in cultured mouse neuroblastoma cells. Neuropharmacology. 1988 Mar;27(3):301–307. doi: 10.1016/0028-3908(88)90048-2. [DOI] [PubMed] [Google Scholar]
  21. Newberry N. R., Cheshire S. H., Gilbert M. J. Evidence that the 5-HT3 receptors of the rat, mouse and guinea-pig superior cervical ganglion may be different. Br J Pharmacol. 1991 Mar;102(3):615–620. doi: 10.1111/j.1476-5381.1991.tb12221.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rajendra S., Lynch J. W., Pierce K. D., French C. R., Barry P. H., Schofield P. R. Mutation of an arginine residue in the human glycine receptor transforms beta-alanine and taurine from agonists into competitive antagonists. Neuron. 1995 Jan;14(1):169–175. doi: 10.1016/0896-6273(95)90251-1. [DOI] [PubMed] [Google Scholar]
  23. Rundström N., Schmieden V., Betz H., Bormann J., Langosch D. Cyanotriphenylborate: subtype-specific blocker of glycine receptor chloride channels. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8950–8954. doi: 10.1073/pnas.91.19.8950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schmieden V., Kuhse J., Betz H. Agonist pharmacology of neonatal and adult glycine receptor alpha subunits: identification of amino acid residues involved in taurine activation. EMBO J. 1992 Jun;11(6):2025–2032. doi: 10.1002/j.1460-2075.1992.tb05259.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sepúlveda M. I., Lummis S. C., Martin I. L. The agonist properties of m-chlorophenylbiguanide and 2-methyl-5-hydroxytryptamine on 5-HT3 receptors in N1E-115 neuroblastoma cells. Br J Pharmacol. 1991 Oct;104(2):536–540. doi: 10.1111/j.1476-5381.1991.tb12464.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Vandenberg R. J., Handford C. A., Schofield P. R. Distinct agonist- and antagonist-binding sites on the glycine receptor. Neuron. 1992 Sep;9(3):491–496. doi: 10.1016/0896-6273(92)90186-h. [DOI] [PubMed] [Google Scholar]
  27. Wakamori M., Ikemoto Y., Akaike N. Effects of two volatile anesthetics and a volatile convulsant on the excitatory and inhibitory amino acid responses in dissociated CNS neurons of the rat. J Neurophysiol. 1991 Dec;66(6):2014–2021. doi: 10.1152/jn.1991.66.6.2014. [DOI] [PubMed] [Google Scholar]
  28. Yakel J. L., Jackson M. B. 5-HT3 receptors mediate rapid responses in cultured hippocampus and a clonal cell line. Neuron. 1988 Sep;1(7):615–621. doi: 10.1016/0896-6273(88)90111-0. [DOI] [PubMed] [Google Scholar]
  29. Yang J., Mathie A., Hille B. 5-HT3 receptor channels in dissociated rat superior cervical ganglion neurons. J Physiol. 1992 Mar;448:237–256. doi: 10.1113/jphysiol.1992.sp019039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Zifa E., Fillion G. 5-Hydroxytryptamine receptors. Pharmacol Rev. 1992 Sep;44(3):401–458. [PubMed] [Google Scholar]

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

RESOURCES