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• W2100059138 endingPage "226" @default.
• W2100059138 startingPage "221" @default.
• W2100059138 abstract "The regulation in expression of human 5-hydroxytryptamine1A (5-HT1A) receptors by agonists and antagonists was studied in a stable transfected Chinese hamster ovary cell line expressing the human 5-HT1A receptor. Receptor density and affinity were measured with [125I]4-(2'-methoxyphenyl)-1-[2'-[N-(2'-pyridinyl)-p-iodobenzamido ]ethyl]piperazine ([125I]p-MPPI), a selective antagonist of 5-HT1A receptors. Treatment of Chinese hamster ovary cells with serotonin or the selective agonist (+/-)-8-hydroxy-N,N-dipropyl-2-aminotetralin stimulated a 2.5-fold increase in receptor density. The antagonists 4-(2'-methoxyphenyl)-1-[2'-[N-(2'-pyridinyl)-p-iodobenzamidoethyl] piperazine, (-)-(S)-pindolol, and spiperone also stimulated up-regulation of receptor expression. Agonist- and antagonist-stimulated up-regulations of receptor expression were mechanistically different. The effect of agonists was inhibited by pertussis toxin, actinomycin D, and cycloheximide. Antagonist-stimulated up-regulation was inhibited by cycloheximide, only partially inhibited by actinomycin D, and not inhibited by pertussis toxin. In the course of identifying potential pathways for coupling of the receptor to activation of transcription, we demonstrated that agonists activate the transcription regulatory factor nuclear factor-kappaB (NF-kappaB). Agonists were found to stimulate degradation of the inhibitory subunit, IkappaB alpha, and to increase the activity of a NF-kappaB-dependent CAT reporter gene. In contrast, the antagonist 4-(2'-methoxyphenyl)-1-[2'-[N-(2'-pyridinyl)-p-iodobenzamidoethyl] piperazine neither elicited degradation of Ikappa-B alpha nor increased reporter activity. Our data suggest that expression of 5-HT1A receptors can be regulated by both agonists and antagonists and that the agonist but not antagonist stimulation occurs concomitantly with activation of NF-kappaB." @default.
• W2100059138 created "2016-06-24" @default.
• W2100059138 creator A5069378252 @default.
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• W2100059138 date "1997-08-01" @default.
• W2100059138 modified "2023-10-13" @default.
• W2100059138 title "5-Hydroxytryptamine_1AReceptor-Mediated Increases in Receptor Expression and Activation of Nuclear Factor-κB in Transfected Chinese Hamster Ovary Cells" @default.
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• W2100059138 doi "https://doi.org/10.1124/mol.52.2.221" @default.
• W2100059138 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9271344" @default.
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