Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Br J Pharmacol
1999 Mar 01;1265:1230-6. doi: 10.1038/sj.bjp.0702402.
Show Gene links
Show Anatomy links
Actions of 3-[2-phosphonomethyl[1,1-biphenyl]-3-yl]alanine (PMBA) on cloned glycine receptors.
Hosie AM
,
Akagi H
,
Ishida M
,
Shinozaki H
.
???displayArticle.abstract???
1. PMBA is a novel antagonist of strychnine-sensitive glycine receptors in the rat spinal cord, however, its mode of action is unknown. The actions of PMBA on rat glycine receptor alpha1 and alpha2 homomers in Xenopus oocytes were studied under two-electrode voltage-clamp. 2. Co-application of PMBA and glycine to both alpha1 and alpha2 homomers yielded inward currents which decayed to a steady-state. Responses rose slowly to the same steady-state amplitude following a 2 min pre-incubation in PMBA. Strychnine, but not picrotoxinin, showed similar antagonism to PMBA. The potency of PMBA was independent of membrane potential between -100 and 0 mV. 3. When tested against EC50 concentrations of glycine, PMBA was almost equally potent on alpha1 (IC50, 406+/-41 nM: Hill coefficient, 1.5+/-0.2) and alpha2 (IC50, 539+/-56 nM; Hill coefficient, 1.4+/-0.2) homomers. 4. PMBA (1-I0 microM) and strychnine (200 nM) reduced the potency of glycine and the amplitude of the maximal agonist response of alpha1 and alpha2 homomers. In 10 microM PMBA, two distinct classes of glycine response were observed on alpha2, only a single class of responses were observed on alpha1. 5. There are similarities in PMBA and strychnine antagonism, although these compounds are structurally distinct. The possibility that PMBA interacts at two binding sites which differ in alpha1 and alpha2 subunits is discussed. PMBA may provide a lead structure for novel antagonists with which to investigate structural differences in glycine receptor at alpha1 and alpha2 subunits.
Akagi,
Functional properties of strychnine-sensitive glycine receptors expressed in Xenopus oocytes injected with a single mRNA.
1991, Pubmed,
Xenbase
Akagi,
Functional properties of strychnine-sensitive glycine receptors expressed in Xenopus oocytes injected with a single mRNA.
1991,
Pubmed
,
Xenbase
Akagi,
Cloning of a glycine receptor subtype expressed in rat brain and spinal cord during a specific period of neuronal development.
1991,
Pubmed
,
Xenbase
Akagi,
Heterogeneity of glycine receptors and their messenger RNAs in rat brain and spinal cord.
1988,
Pubmed
,
Xenbase
Aprison,
Identification of a second glycine-like fragment on the strychnine molecule.
1995,
Pubmed
Becker,
Glycine receptor heterogeneity in rat spinal cord during postnatal development.
1988,
Pubmed
Constanti,
The "mixed" effect of picrotoxin on the GABA dose/conductance relation recorded from lobster muscle.
1978,
Pubmed
Fujimoto,
Dual mechanisms of GABAA response inhibition by beta-lactam antibiotics in the pyramidal neurones of the rat cerebral cortex.
1995,
Pubmed
Grenningloh,
The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors.
,
Pubmed
Grenningloh,
Cloning and expression of the 58 kd beta subunit of the inhibitory glycine receptor.
1990,
Pubmed
,
Xenbase
Karlin,
Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins.
1995,
Pubmed
Krogsgaard-Larsen,
Glycine antagonists structurally related to muscimol, THIP, or isoguvacine.
1982,
Pubmed
Kuhse,
Identification and functional expression of a novel ligand binding subunit of the inhibitory glycine receptor.
1990,
Pubmed
,
Xenbase
Kuhse,
The inhibitory glycine receptor: architecture, synaptic localization and molecular pathology of a postsynaptic ion-channel complex.
1995,
Pubmed
Kuhse,
A single amino acid exchange alters the pharmacology of neonatal rat glycine receptor subunit.
1990,
Pubmed
,
Xenbase
Langosch,
Conserved quaternary structure of ligand-gated ion channels: the postsynaptic glycine receptor is a pentamer.
1988,
Pubmed
Langosch,
Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia.
1994,
Pubmed
,
Xenbase
Lynch,
Mutations affecting the glycine receptor agonist transduction mechanism convert the competitive antagonist, picrotoxin, into an allosteric potentiator.
1995,
Pubmed
Malosio,
Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain.
1991,
Pubmed
Marvizón,
The glycine receptor: pharmacological studies and mathematical modeling of the allosteric interaction between the glycine- and strychnine-binding sites.
1986,
Pubmed
Pullan,
Comparison of binding at strychnine-sensitive (inhibitory glycine receptor) and strychnine-insensitive (N-methyl-D-aspartate receptor) glycine binding sites.
1992,
Pubmed
Rajendra,
The unique extracellular disulfide loop of the glycine receptor is a principal ligand binding element.
1995,
Pubmed
Rundström,
Cyanotriphenylborate: subtype-specific blocker of glycine receptor chloride channels.
1994,
Pubmed
Saitoh,
A novel antagonist, phenylbenzene omega-phosphono-alpha-amino acid, for strychnine-sensitive glycine receptors in the rat spinal cord.
1994,
Pubmed
Schmieden,
Pharmacology of the inhibitory glycine receptor: agonist and antagonist actions of amino acids and piperidine carboxylic acid compounds.
1995,
Pubmed
,
Xenbase
Schmieden,
Mutation of glycine receptor subunit creates beta-alanine receptor responsive to GABA.
1993,
Pubmed
,
Xenbase
Schmieden,
Functional expression in Xenopus oocytes of the strychnine binding 48 kd subunit of the glycine receptor.
1989,
Pubmed
,
Xenbase
Schmieden,
Agonist pharmacology of neonatal and adult glycine receptor alpha subunits: identification of amino acid residues involved in taurine activation.
1992,
Pubmed
,
Xenbase
Smart,
Studies on the mechanism of action of picrotoxinin and other convulsants at the crustacean muscle GABA receptor.
1986,
Pubmed
Takahashi,
Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels.
1992,
Pubmed
,
Xenbase
Tokutomi,
What confers specificity on glycine for its receptor site?
1989,
Pubmed
Uchida,
The differential antagonism by bicuculline and SR95531 of pentobarbitone-induced currents in cultured hippocampal neurons.
1996,
Pubmed
Ueno,
Bicuculline and gabazine are allosteric inhibitors of channel opening of the GABAA receptor.
1997,
Pubmed
Vandenberg,
Antagonism of ligand-gated ion channel receptors: two domains of the glycine receptor alpha subunit form the strychnine-binding site.
1992,
Pubmed
Vandenberg,
Distinct agonist- and antagonist-binding sites on the glycine receptor.
1992,
Pubmed
Werman,
Inhibition of motoneurones by iontophoresis of glycine.
1967,
Pubmed
Wooltorton,
Pharmacological and physiological characterization of murine homomeric beta3 GABA(A) receptors.
1997,
Pubmed
,
Xenbase
