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. 1993 May;109(1):200–206. doi: 10.1111/j.1476-5381.1993.tb13554.x

Pharmacology of GABA rho 1 and GABA alpha/beta receptors expressed in Xenopus oocytes and COS cells.

T Kusama 1, C E Spivak 1, P Whiting 1, V L Dawson 1, J C Schaeffer 1, G R Uhl 1
PMCID: PMC2175610  PMID: 8388298

Abstract

1. The rho 1 protein, which we previously cloned from retina, assembles as a homooligomer that transduces the binding of gamma-aminobutyric acid (GABA) into robust chloride currents. However, its insensitivity to bicuculline, pentobarbitone and benzodiazepines, all potent agents at typical GABAA receptors, suggested that it may react atypically to other GABA agonists and antagonists. 2. cDNAs for the rho 1 and the alpha 5 beta 1 receptors for GABA were expressed as homo- and heterooligomers, respectively, in Xenopus oocytes. The selectivities of the respective receptors for various agonists were investigated using concentration-response experiments in voltage clamped cells. 3. The most potent agonists at the rho 1 receptor were trans-4-aminocrotonic acid (TACA) > GABA > muscimol; at the alpha 5 beta 1 receptor the rank order was muscimol > GABA > 4,5,6,7-tetrahydroisoxazole[4,5-c]pyridine-3-ol (THIP). The most specific agonists were cis-(2-(aminomethyl)-cyclopropyl-carboxylic acid (CAMP) and THIP for the rho 1 and the alpha 5 beta 1 receptors, respectively. 4. Comparing GABA, TACA and cis-aminocrotonic acid (CACA) at rho 1 receptors expressed in COS cells gave results almost indistinguishable from those found at oocytes; the pharmacology of rho 1 seems independent of the expression system. 5. Agonists THIP, piperidine-4-sulphonic acid (P4S), and isoguvacine, whose C-C-C-N chains are constrained by rings into a folded conformation and were potent at the alpha 5 beta 1 receptor, were among the weakest at the rho 1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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