N-methyl-D-aspartate (NMDA) stimulates release of alpha-MSH from the rat hypothalamus through release of nitric oxide.
Superfusion of rat hypothalamic slices with 10(-4) M N-methyl-D-aspartic acid (NMDA) resulted in increased release of alpha-melanocyte-stimulating hormone (alpha-MSH). Peptide release was blocked by 10(-6) M NG-nitro-L-arginine methyl ester (L-NAME) a specific competitive inhibitor of nitric oxide synthase but not by the inactive enantiomer D-NAME at 10(-6) M. The inhibition by L-NAME was reversed by the addition of 10(-5) mM L-arginine, an excess of enzyme substrate. Release of nitric oxide products into tissue superfusates was stimulated by a 50 mM concentration of potassium ions and by 10(-4) M NMDA. Potassium-stimulated release was blocked by L-NAME. Basal, potassium-stimulated and NMDA-stimulated release of nitric oxide products were significantly inhibited by the NMDA-receptor antagonist D(-)-2-amino-5-phosphopentanoic acid (AP5) at 10(-4) M and by the NMDA-channel blocker ketamine at 10(-4) M. We conclude that nitric oxide mediates the stimulatory action of glutamic acid on the release of alpha-MSH from the rat hypothalamus.
Wayman
C P
CP
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Health Park, Cardiff, UK.
Pike
N V
NV
Wilson
J F
JF
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000521:alpha-MSH / Q000378:metabolism*
D009569:Nitric Oxide; D000521:alpha-MSH; D016202:N-Methylaspartate; D007649:Ketamine; D015763:2-Amino-5-phosphonovalerate; D001120:Arginine; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester