Abstract
1. The structural requirements for activation of the glycine receptor were studied in isolated ventromedial hypothalamic neurones of rats by use of a 'concentration-clamp' technique under single-electrode voltage-clamp conditions. 2. alpha-Amino acids (L-alpha-alanine, and D-alpha-alanine, and L-serine), and glycine-methylester, glycine-ethylester and beta-amino acids (beta-alanine and taurine) produced a transient inward Cl- current, which was similar to that induced by glycine. 3. The responses to individual alpha- and beta-amino acids were selectively antagonized by strychnine, but were not affected by bicuculline, picrotoxin or the taurine antagonist, TAG (6-aminomethyl-3-methyl-4H,1,2,4-benzothiadiazine-1,1-dioxide hydrochloride), suggesting that alpha- and beta-amino acids activate the same glycine receptor. 4. beta-Amino acids were slightly more potent than the alpha-amino acids in causing cross-desensitization of the glycine response. 5. From the results of the structure-activity analysis of the optical isomers of alpha-alanine, serine and cysteine, a tentative structure of the glycine receptor is proposed.
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- Akaike N., Hattori K., Oomura Y., Carpenter D. O. Bicuculline and picrotoxin block gamma-aminobutyric acid-gated Cl- conductance by different mechanisms. Experientia. 1985 Jan 15;41(1):70–71. doi: 10.1007/BF02005880. [DOI] [PubMed] [Google Scholar]
- Akaike N., Inoue M., Krishtal O. A. 'Concentration-clamp' study of gamma-aminobutyric-acid-induced chloride current kinetics in frog sensory neurones. J Physiol. 1986 Oct;379:171–185. doi: 10.1113/jphysiol.1986.sp016246. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bristow D. R., Bowery N. G., Woodruff G. N. Light microscopic autoradiographic localisation of [3H]glycine and [3H]strychnine binding sites in rat brain. Eur J Pharmacol. 1986 Jul 31;126(3):303–307. doi: 10.1016/0014-2999(86)90062-2. [DOI] [PubMed] [Google Scholar]
- Constanti A. The "mixed" effect of picrotoxin on the GABA dose/conductance relation recorded from lobster muscle. Neuropharmacology. 1978 Mar;17(3):159–167. doi: 10.1016/0028-3908(78)90095-3. [DOI] [PubMed] [Google Scholar]
- Curtis D. R., Duggan A. W., Felix D., Johnston G. A., McLennan H. Antagonism between bicuculline and GABA in the cat brain. Brain Res. 1971 Oct 8;33(1):57–73. doi: 10.1016/0006-8993(71)90305-2. [DOI] [PubMed] [Google Scholar]
- Curtis D. R., Hösli L., Johnston G. A. A pharmacological study of the depression of spinal neurones by glycine and related amino acids. Exp Brain Res. 1968;6(1):1–18. doi: 10.1007/BF00235443. [DOI] [PubMed] [Google Scholar]
- DeFeudis F. V. Glycine-receptors in the vertebrate central nervous system. Acta Physiol Lat Am. 1977;27(4):131–145. [PubMed] [Google Scholar]
- Graham D., Pfeiffer F., Simler R., Betz H. Purification and characterization of the glycine receptor of pig spinal cord. Biochemistry. 1985 Feb 12;24(4):990–994. doi: 10.1021/bi00325a027. [DOI] [PubMed] [Google Scholar]
- Hattori K., Akaike N., Oomura Y., Kuraoka S. Internal perfusion studies demonstrating GABA-induced chloride responses in frog primary afferent neurons. Am J Physiol. 1984 Mar;246(3 Pt 1):C259–C265. doi: 10.1152/ajpcell.1984.246.3.C259. [DOI] [PubMed] [Google Scholar]
- Ishizuka S., Hattori K., Akaike N. Separation of ionic currents in the somatic membrane of frog sensory neurons. J Membr Biol. 1984;78(1):19–28. doi: 10.1007/BF01872528. [DOI] [PubMed] [Google Scholar]
- Johnson J. W., Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature. 1987 Feb 5;325(6104):529–531. doi: 10.1038/325529a0. [DOI] [PubMed] [Google Scholar]
- Johnston G. A., Iversen L. L. Glycine uptake in rat central nervous system slices and homogenates: evidence for different uptake systems in spinal cord and cerebral cortex. J Neurochem. 1971 Oct;18(10):1951–1961. doi: 10.1111/j.1471-4159.1971.tb09601.x. [DOI] [PubMed] [Google Scholar]
- Johnston G. A., Krogsgaard-Larsen P., Stephanson A. L., Twitchin B. Inhibition of the uptake of GABA and related amino acids in rat brain slices by the optical isomers of nipecotic acid. J Neurochem. 1976 May;26(5):1029–1032. doi: 10.1111/j.1471-4159.1976.tb06488.x. [DOI] [PubMed] [Google Scholar]
- Kaneda M., Nakamura H., Akaike N. Mechanical and enzymatic isolation of mammalian CNS neurons. Neurosci Res. 1988 Apr;5(4):299–315. doi: 10.1016/0168-0102(88)90032-6. [DOI] [PubMed] [Google Scholar]
- Kishimoto H., Simon J. R., Aprison M. H. Determination of the equilibrium dissociation constants and number of glycine binding sites in several areas of the rat central nervous system, using a sodium-independent system. J Neurochem. 1981 Oct;37(4):1015–1024. doi: 10.1111/j.1471-4159.1981.tb04489.x. [DOI] [PubMed] [Google Scholar]
- Krogsgaard-Larsen P., Johnston G. A., Curtis D. R., Game C. J., McCulloch R. M. Structure and biological activity of a series of conformationally restricted analogues of GABA. J Neurochem. 1975 Dec;25(6):803–809. doi: 10.1111/j.1471-4159.1975.tb04411.x. [DOI] [PubMed] [Google Scholar]
- Martin G. E., Bendesky R. J., Williams M. Further evidence for selective antagonism of taurine by 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide. Brain Res. 1981 Dec 21;229(2):530–535. doi: 10.1016/0006-8993(81)91017-9. [DOI] [PubMed] [Google Scholar]
- Okamoto K., Kimura H., Sakai Y. Evidence for taurine as an inhibitory neurotransmitter in cerebellar stellate interneurons: selective antagonism by TAG (6-aminomethyl-3-methyl-4H,1,2,4-benzothiadiazine-1,1-dioxide). Brain Res. 1983 Apr 11;265(1):163–168. doi: 10.1016/0006-8993(83)91350-1. [DOI] [PubMed] [Google Scholar]
- Pycock C. J., Kerwin R. W. The status of glycine as a supraspinal neurotransmitter. Life Sci. 1981 Jun 15;28(24):2679–2686. doi: 10.1016/0024-3205(81)90168-5. [DOI] [PubMed] [Google Scholar]
- Wilkin G. P., Csillag A., Balázs R., Kingsbury A. E., Wilson J. E., Johnson A. L. Localization of high affinity [3H]glycine transport sites in the cerebellar cortex. Brain Res. 1981 Jul 6;216(1):11–33. doi: 10.1016/0006-8993(81)91275-0. [DOI] [PubMed] [Google Scholar]
- Yakushiji T., Tokutomi N., Akaike N., Carpenter D. O. Antagonists of GABA responses, studied using internally perfused frog dorsal root ganglion neurons. Neuroscience. 1987 Sep;22(3):1123–1133. doi: 10.1016/0306-4522(87)92987-3. [DOI] [PubMed] [Google Scholar]
- Yarbrough G. G., Singh D. K., Taylor D. A. Neuropharmacological characterization of a taurine antagonist. J Pharmacol Exp Ther. 1981 Dec;219(3):604–613. [PubMed] [Google Scholar]