Characteristics of NMDA receptors that stimulate release of hypothalamic alpha-MSH.
N-methyl-D-aspartic acid (NMDA) 10(-4) M stimulated release of immunoreactive alpha-melanocyte-stimulating hormone (alpha-MSH) from superfused slices of rat hypothalamus through receptors which shared common features with other central NMDA-type glutamate receptors. The receptors possessed inhibitory sites for both Mg2+ and ketamine; basal and NMDA-stimulated alpha-MSH release was reduced by high (5 mM) Mg2+ ion concentrations and by 10(-4) M ketamine, whilst use of Mg(2+)-free media led to a prolongation of the NMDA-stimulated response. The receptors were also shown to possess an allosteric glycine site. The glycine site agonist D-serine 10(-4) M potentiated basal and NMDA-stimulated alpha-MSH release whilst the antagonist, 7-chlorokynurenic acid 10(-4) M, reduced NMDA-stimulated release, an effect which was partially reversed by 10(-4) M D-serine.
Wayman
C P
CP
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Wilson
J F
JF
D000818:Animals; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology; D007700:Kinetics; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012694:Serine / Q000494:pharmacology; D000521:alpha-MSH / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D000521:alpha-MSH; D016202:N-Methylaspartate; D007649:Ketamine; D007736:Kynurenic Acid; D008274:Magnesium; C057013:7-chlorokynurenic acid