Serotonergic modulation of L-glutamic acid-evoked release of endogenous norepinephrine from rat hypothalamus.
Hypothalamic slices (400 mu) from male Sprague-Dawley rats were perfused with a Mg+(+)-free medium containing nomifensine (10 microM) and tyrosine (50 microM). Spontaneous release of endogenous norepinephrine (NE), measured by high-performance liquid chromatography-electrochemical detection, averaged 102 +/- 13 (N = 76) fmol/mg of protein/3 min. L-Glutamic acid (L-GLU) (1 mM) more than doubled the rate of NE release. Preincubation with serotonin (5-HT) (0.1-10 microM) produced no change in spontaneous NE release but caused a concentration-dependent decrease of L-GLU-induced NE release with a maximal reduction of about 60 to 70%. 2-Methylserotonin, a 5-HT3 receptor agonist (0.07-10 microM), mimicked the 5-HT response. A highly selective 5-HT3 receptor antagonist, (3 alpha-tropanyl)1H-indole-3-carboxylic acid ester, 1 nM, inhibited the effect of both agonists. Neither ritanserin (1 microM) nor methylsergide (1 microM) modified either spontaneous or 1 mM L-GLU-evoked release of NE. However, if added to the superfusion medium simultaneously with 5-HT, they potentiated significantly the inhibition produced by 5-HT. Alpha-methylserotonin (1 microM) if added alone to the perfusion medium had no effect on 1 mM L-GLU-evoked release of NE but reversed the inhibition induced by 1 microM 2-methylserotonin. These observations provide direct evidence of a dual modulation by 5-HT of L-GLU-evoked release of endogenous NE from slices of rat hypothalamus: An inhibition mediated by 5-HT3 receptors and an opposing action mediated by receptors of the 5-HT1C/2 type.
Goldfarb
J
J
Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, New York.
Walcott
J
J
Blandina
P
P
D000818:Animals; D005971:Glutamates / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D009638:Norepinephrine