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• W2085887265 abstract "1 Stimulation of phosphoinositide hydrolysis by human mGlu1α (HmGlu1α) was examined in a non-neuronal cell line (AV12-664) co-expressing both HmGlu1α and a rat glutamate/aspartate transporter (GLAST). 2 Desensitization of HmGlu1α could be elicited by inhibition of the GLAST transporter with the glutamate uptake inhibitor, L-trans-pyrrolidine-2, 4-dicarboxylic acid (trans-PDC). Maximal inhibition of HmGlu1α-mediated phosphoinositide hydrolysis was induced upon 24 h pretreatment with trans-PDC. The concentration of glutamate in the extracellular medium also rose significantly in cells pretreated with trans-PDC. Glutamate levels increased upon incubation with trans-PDC in a time-dependent manner, with maximal glutamate levels attained after 24 h incubation with trans-PDC. 3 The time required for desensitization of HmGlu1α by trans-PDC was compared to the time course for desensitization elicited by the direct-acting mGlu receptor agonists, 1-aminocyclopentane-1S, 3R-dicarboxylic acid (1S, 3R-ACPD) and (R, S)-3, 5-dihydroxyphenylglycine (3, 5-DHPG). Both direct-acting mGlu receptor agonists elicited desensitization of HmGlu1α more rapidly than did trans-PDC, with maximal inhibition of agonist-induced phosphoinositide hydrolysis upon 12 h pretreatment. Agonist-induced desensitization could be fully reversed upon washout of agonist for 12 h. 4 Both mGlu receptor agonist- and trans-PDC-induced desensitization of HmGlu1α could be blocked by inclusion of (+)-α-methyl-4-carboxyphenylglycine (MCPG), an mGlu receptor antagonist, in the pretreatment medium. 5 Agonist-stimulated phosphoinositide hydrolysis by HmGlu1α was found to parallel closely agonist-induced desensitization of HmGlu1α. Thus, the EC50 values for 1S, 3R-ACPD- and 3, 5-DHPG-stimulated phosphoinositide hydrolysis were similar to the EC50 values for eliciting desensitization of HmGlu1α. 6 These studies demonstrate desensitization of recombinant human mGlu1α receptor in a non-neuronal cell line in which the receptor can be regulated by direct activation or by manipulation of glutamate transporter activity. Desensitization of HmGlu1α was found to be mediated by activation of the receptor since the mGlu receptor antagonist, MCPG, blocked both mGlu receptor agonist- and trans-PDC-induced desensitization of HmGlu1α. Furthermore, agonist-induced desensitization of HmGlu1α was found to parallel receptor-mediated stimulation of phosphoinositide hydrolysis." @default.
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• W2085887265 date "1996-07-01" @default.
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• W2085887265 title "Pharmacological characterization of desensitization in a human mGlulα-expressing non-neuronal cell line co-transfected with a glutamate transporter" @default.
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• W2085887265 doi "https://doi.org/10.1111/j.1476-5381.1996.tb15574.x" @default.
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