| trans-4-Amino-2-methylbut-2-enoic acid (2-MeTACA) and (+/-)-trans-2-aminomethylcyclopropanecarboxylic acid ((+/-)-TAMP) can differentiate rat rho3 from human rho1 and rho2 recombinant GABA(C) receptors. | |
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MedLine Citation:
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PMID: 11861315 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. This study investigated the effects of a number of GABA analogues on rat rho3 GABA(C) receptors expressed in Xenopus oocytes using 2-electrode voltage clamp methods. 2. The potency order of agonists was muscimol (EC(50)=1.9 +/- 0.1 microM) (+)-trans-3-aminocyclopentanecarboxylic acids ((+)-TACP; EC(50)=2.7 +/- 0.9 microM) trans-4-aminocrotonic acid (TACA; EC(50)=3.8 +/-0.3 microM) GABA (EC(50)=4.0 +/- 0.3 microM) > thiomuscimol (EC(50)=24.8 +/- 2.6 microM) > (+/-)-cis-2-aminomethylcyclopropane-carboxylic acid ((+/-)-CAMP; EC(50)=52.6 +/-8.7 microM) > cis-4-aminocrotonic acid (CACA; EC(50)=139.4 +/- 5.2 microM). 3. The potency order of antagonists was (+/-)-trans-2-aminomethylcyclopropanecarboxylic acid ((+/-)-TAMP; K(B)=4.8+/-1.8 microM) (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA; K(B)=4.8 +/-0.8 microM) > (piperidin-4-yl)methylphosphinic acid (P4MPA; K(B)=10.2+/-2.3 microM) 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP; K(B)=10.2+/-0.3 microM) imidazole-4-acetic acid (I4AA; K(B)=12.6+/-2.7 microM) > 3-aminopropylphosphonic acid (3-APA; K(B)=35.8+/-13.5 microM). 4. trans-4-Amino-2-methylbut-2-enoic acid (2-MeTACA; 300 microM) had no effect as an agonist or an antagonist indicating that the C2 methyl substituent is sterically interacting with the ligand-binding site of rat rho3 GABA(C) receptors. 5. 2-MeTACA affects rho1 and rho2 but not rho3 GABA(C) receptors. In contrast, (plus minus)-TAMP is a partial agonist at rho1 and rho2 GABA(C) receptors, while at rat rho3 GABA(C) receptors it is an antagonist. Thus, 2-MeTACA and (+/-)-TAMP could be important pharmacological tools because they may functionally differentiate between rho1, rho2 and rho3 GABA(C) receptors in vitro. |
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Authors:
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Jimmy Vien; Rujee K Duke; Kenneth N Mewett; Graham A R Johnston; Ryuzo Shingai; Mary Chebib |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 135 ISSN: 0007-1188 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2002 Feb |
Date Detail:
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Created Date: 2002-03-06 Completed Date: 2002-12-26 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 883-90 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, University of Sydney, NSW 2006, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Butyric Acid / pharmacology* Butyric Acids Carboxylic Acids / pharmacology* Cyclopropanes / pharmacology* GABA Agonists / pharmacology GABA Antagonists / pharmacology Humans Ion Channels / drug effects, physiology Oocytes / drug effects, metabolism, physiology Patch-Clamp Techniques Protein Subunits Rats Receptors, GABA / drug effects*, physiology Recombinant Proteins Stereoisomerism Structure-Activity Relationship Xenopus laevis |
| Chemical | |
Reg. No./Substance:
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0/2-aminomethylcyclopropanecarboxylic acid; 0/4-Amino-2-methylbut-2-enoic acid; 0/Butyric Acids; 0/Carboxylic Acids; 0/Cyclopropanes; 0/GABA Agonists; 0/GABA Antagonists; 0/GABA-C receptor; 0/Ion Channels; 0/Protein Subunits; 0/Receptors, GABA; 0/Recombinant Proteins; 107-92-6/Butyric Acid |
| Comments/Corrections | |
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