| 11879973 |
Ratra GS, Erkkila BE, Weiss DS, Casida JE: Unique insecticide specificity of human homomeric rho 1 GABA (C) receptor. . Toxicol Lett. 2002 Mar 24;129(1-2):47-53.
Several convulsants and major insecticides block the gamma-aminobutyric acid (GABA)-gated chloride channel in brain on binding to the GABA (A) receptor. The GABA (C) receptor, important in retina and present in brain, is also coupled to a chloride channel and is therefore a potential target for toxicant action examined here in radioligand binding and electrophysiological experiments. Human homomeric rho 1 GABA (C) receptor expressed in human embryonic kidney cells (HEK293) undergoes specific and saturable high-affinity binding of 4-n-[3H] propyl-4' -ethynylbicycloorthobenzoate ([3H] EBOB) using a cyano analog (CNBOB) to determine non-specific binding. This GABA (C) rho 1 receptor is very sensitive to CNBOB and lindane relative to alpha-endosulfan, tert-butylbicyclophosphorothionate, picrotoxinin and fipronil (IC (50) values of 23, 91, 800, 1080, 4000 and > 10000 nM, respectively, in displacing [3H] EBOB). A similar potency sequence (except for picrotoxinin) is observed for inhibition of GABA-induced currents of rho 1 receptor expressed in Xenopus oocytes. The present study does not consider rho 2 homomeric and rho 1 rho 2 heteromeric GABA (C) receptors which are known to be more sensitive than rho 1 to picrotoxinin. The inhibitor sensitivity and specificity of this rho 1 GABA (C) receptor differ greatly from those of human homomeric beta 3 and native GABA (A) receptors. |
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