Release of endogenous norepinephrine from rat hypothalamus by stimulation of N-methyl-D-aspartic acid receptors.
Release of endogenous dopamine and norepinephrine (NE) from rat hypothalamic slices superfused with Mg(++)-free medium in the presence of nomifensine and tyrosine was measured by high-performance liquid chromatography coupled to an electrochemical detector. Superfusion with L-glutamic acid or N-methyl-D-aspartic acid elicited a concentration-dependent release of NE but not of dopamine. The release of NE was transient, returning toward basal values despite the continued presence of the amino acid. Superfusion with 20 mM K+ caused a release of NE that declined at a slower rate. Mg++, DL-2-amino-5-phosphonopentanoic acid and MK-801 (D-5-methyl-10,11,dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine maleate), but not 6-cyano-7-nitroquinoxaline-2,3-dione, inhibited the L-glutamic acid-evoked release of NE. The release of NE by L-glutamic acid was virtually abolished by tetrodotoxin and by elimination of Ca++ from and inclusion of 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid in the superfusion medium. Repeated L-glutamic acid applications displayed a decreased response, whereas repeated exposure to 20 mM K+ did not. Exposure to L-glutamic acid in the absence of Ca++ (plus 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid) or in the presence of DL-2-amino-5-phosphonopentanoic acid did not reduce the effects seen on subsequent exposure to L-glutamic acid. Exposure to L-glutamic acid in the absence of Mg++ reduced the effect of a subsequent exposure to L-glutamic acid. These observations provide evidence for an indirect modulation of rat hypothalamic endogenous NE by the N-methyl-D-aspartate receptor.
Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, NY.
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Blandina
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Johnson
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Walcott
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Goldfarb
D000818:Animals; D046508:Culture Techniques; D004298:Dopamine / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D015222:Sodium Channels / Q000187:drug effects
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D018698:Glutamic Acid; D011189:Potassium Chloride; D008274:Magnesium; D004298:Dopamine; D009638:Norepinephrine