Serotonergic modulation of the release of endogenous norepinephrine from rat hypothalamic slices.
Ca+(+)-dependent release of endogenous norepinephrine (NE) and dopamine from superfused rat hypothalamic slices was stimulated by 40 mM K+. 20 mM K+ released only NE. Two consecutive exposures to 20 mM K+ (S1 and S2, respectively) produced NE release of similar magnitude (S2/S1 = 1.03 +/- 0.08). Serotonin (5-HT), 3 to 10 microM, in the presence of methylsergide or ritanserin (antagonists at 5-HT1-like and 5-HT2 receptors), caused a concentration-dependent decrease of K(+)-evoked NE release. 5-HT alone did not alter K(+)-evoked NE release. 2-Methyl-serotonin, 2-methyl-5-hydroxytryptamine, 3 to 10 microM (a selective 5-HT3 agonist), mimicked the 5-HT response in the presence and in the absence of ritanserin. A highly selective 5-HT3 antagonist, (3 alpha-tropanyl)1H-indole-3-carboxylic acid ester (ICS 205-930), 1 nM, inhibited the effect of both agonists. The isomers of another highly selective 5-HT3 antagonist, zacopride, inhibited the effect of 2-methyl-serotonin, 2-methyl-5-hydroxytryptamine, at a concentration range, 0.03 to 20 nM, characteristic of their interaction with 5-HT3 receptors. alpha-Methyl-serotonin, alpha-methyl-5-hydroxytryptamine, a selective 5-HT1-like/5-HT2 agonist, failed to affect the K(+)-evoked NE release, but antagonized the effect of 2-methyl-serotonin, 2-methyl-5-hydroxytryptamine. These observations provide direct evidence that, in rat hypothalamus, 5-HT modulates release of endogenous NE through activation of 5-HT3 and, possibly, 5-HT1C receptors.
Blandina
P
P
Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, New York.
Goldfarb
J
J
Walcott
J
J
Green
J P
JP
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000145:classification / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D011188:Potassium; D004298:Dopamine; D009638:Norepinephrine