Mechanism underlying the effect of pregnenolone sulfate on the kainate-induced current in cultured chick spinal cord neurons.
The effect of the neurosteroid pregnenolone sulfate on the kainate receptor-mediated response was studied in cultured chick spinal cord neurons using the whole-cell voltage-clamp recording technique. Pregnenolone sulfate rapidly and reversibly inhibits the kainate-induced current in a dose-dependent manner, with an EC50 of 67 microM and maximal inhibition of 38%. Inhibition by pregnenolone sulfate of the kainate response is not attenuated by increasing concentrations of kainate, suggesting that the blocking action of pregnenolone sulfate is non-competitive. Antagonism of the kainate response by pregnenolone sulfate is neither agonist- nor voltage-dependent, indicating that pregnenolone sulfate does not act as an open-channel blocker. Furthermore, our results demonstrate that pregnenolone sulfate and 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466; a potent non-competitive kainate antagonist) do not act through a common site.
Wu
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FS
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC. fongsen@mail.ncku.edu.tw
Chen
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SC
D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000494:pharmacology; D002478:Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007608:Kainic Acid; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011284:Pregnenolone / Q000494:pharmacology*; D018092:Kainic Acid Receptors / Q000819:agonists / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology*
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D011284:Pregnenolone; D018092:Kainic Acid Receptors; C018370:pregnenolone sulfate; C061950:GYKI 52466