Journal
NEUROSCIENCE LETTERS
Volume 376, Issue 1, Pages 60-65Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2004.11.024
Keywords
GABA(C) receptor; GABA rho subunits; white perch retina; TPMPA; beta-alanine; taurine; glycine
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Funding
- NEI NIH HHS [EY 014557, EY-01792, EY-06516, EY-12028] Funding Source: Medline
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GABA(C) receptors, expressed predominantly in vertebrate retina, are thought to be formed mainly by GABA rho subunits. Five GABA rho subunits have been cloned from white perch retina, four of which form functional homooligomeric receptors when expressed in Xenopus oocytes. These rho subtypes, classified as rho1A, rho1B, rho2A and rho2B receptors based on amino acid sequence alignment, exhibit distinct temporal and pharmacological properties. To examine further the pharmacological proper-ties associated with the various p receptor subtypes, we investigated the effects of a selective GABAC receptor antagonist, TPMPA, on the GABA-mediated activity of receptors formed in Xenopus oocytes by the four GABA p, subunits. In addition, we recorded the activation profiles of P-alanine, taurine, and glycine, three amino acids that modulate neuronal activity in various parts of the CNS and are purported to be p receptor agonists. TPMPA effectively inhibited GABA-elicited responses on A-type receptors, whereas B-type receptors exhibited a relatively low sensitivity to the drug. A-type and B-type receptors also displayed distinctly different reactions to agonists. Both taurine and glycine-activated the B-type receptors, whereas these agents had no detectable effect on A-type receptors. Similarly, beta-alanine evoked large responses from B-type receptors, but was far less effective on A-type receptors. These results indicate that, in addition to the characteristic response properties identified previously, there is a pattern of pharmacological reactions that further distinguishes the A- and B-subtypes of GABA rho receptor. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
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