Endogenous glutamate stimulates release of alpha-melanocyte-stimulating hormone from the rat hypothalamus.
Release of alpha-melanocyte-stimulating hormone (alpha-MSH) and glutamic acid was quantified from superfused slices of rat hypothalamus. Application of L-glutamic acid 10(-4) M failed to evoke release of alpha-MSH but, in the presence of 10(-4) M dihydrokainic acid (DHK) an inhibitor of glutamate uptake systems, caused significant stimulation of release. DHK caused gradual and sustained increases in both alpha-MSH and glutamate release. That in alpha-MSH was blocked by 10(-4) M DL-2-amino-5-phosphopentanoic acid, a competitive N-methyl-D-aspartic acid (NMDA)-type glutamate receptor antagonist. We conclude that hypothalamic glutamate is subject to rapid uptake through mechanisms blocked by DHK and that alpha-MSH release is stimulated by endogenous and exogenous glutamate through NMDA-type receptors.
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
C P
CP
Wayman
J F
JF
Wilson
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D005971:Glutamates / Q000378:metabolism / Q000502:physiology*; D018698:Glutamic Acid; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D011333:Pro-Opiomelanocortin / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000521:alpha-MSH / Q000378:metabolism*
D005971:Glutamates; D018698:Glutamic Acid; C020889:dihydrokainic acid; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D015763:2-Amino-5-phosphonovalerate; D007608:Kainic Acid