PT  - JOURNAL ARTICLE
AU  - Mijeong Park-Chung
AU  - Fong-Sen Wu
AU  - Robert H. Purdy
AU  - Andrew A. Malayev
AU  - Terrell T. Gibbs
AU  - David H. Farb
TI  - Distinct Sites for Inverse Modulation of<em>N</em>-Methyl-<span class="sc">d</span>-Aspartate Receptors by Sulfated Steroids
AID  - 10.1124/mol.52.6.1113
DP  - 1997 Dec 01
TA  - Molecular Pharmacology
PG  - 1113--1123
VI  - 52
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/52/6/1113.short
4100  - http://molpharm.aspetjournals.org/content/52/6/1113.full
SO  - Mol Pharmacol1997 Dec 01; 52
AB  - 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.