TY - JOUR T1 - Distinct Sites for Inverse Modulation of<em>N</em>-Methyl-<span class="sc">d</span>-Aspartate Receptors by Sulfated Steroids JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1113 LP - 1123 DO - 10.1124/mol.52.6.1113 VL - 52 IS - 6 AU - Mijeong Park-Chung AU - Fong-Sen Wu AU - Robert H. Purdy AU - Andrew A. Malayev AU - Terrell T. Gibbs AU - David H. Farb Y1 - 1997/12/01 UR - http://molpharm.aspetjournals.org/content/52/6/1113.abstract N2 - Steroid sulfation occurs in nervous tissue and endogenous sulfated steroids can act as positive or negative modulators ofN-methyl-d-aspartate (NMDA) receptor function. In the current study, structure-activity relationships for sulfated steroids were examined in voltage-clamped chick spinal cord and rat hippocampal neurons in culture and in Xenopus laevis oocytes expressing NR1100 and NR2A subunits. The ability of pregnenolone sulfate (a positive modulator) and epipregnanolone sulfate (a negative modulator) to compete with each another, as well as with other known classes of NMDA receptor modulators, was examined. The results show that steroid positive and negative modulators act at specific, extracellularly directed sites that are distinct from one another and from the spermine, redox, glycine, Mg2+, MK-801, and arachidonic acid sites. Sulfated steroids are effective as modulators of ongoing glutamate-mediated synaptic transmission, which is consistent with their possible role as endogenous neuromodulators in the CNS. ER -