Pharmacological characterization of alpha 2-adrenoceptor regulated serotonin release in the rat hippocampus.
The purpose of the present study was to confirm the functional regulation by alpha 2-adrenoceptors of the release of serotonin (5-HT) from the rat hippocampus in vivo. Under several pharmacological conditions, extracellular levels of 5-HT were estimated by assaying its concentrations in the perfusate by high performance liquid chromatography with electrochemical detection. Extracellular 5-HT in the hippocampus was reduced by tetrodotoxin (10 microM) co-perfusion, but increased by perfusion of a selective 5-HT re-uptake inhibitor, fluoxetine (10 microM). Addition of potassium (K+, 120 mM) to the perfusion fluid evoked an approximately 3-fold increase in 5-HT release. When the alpha 2-adrenoceptor agonist UK14,304 (0.1-10 microM) was added to the perfusion solution, the K(+)-evoked 5-HT release was significantly inhibited in a concentration-dependent manner. This inhibitory action of UK14,304 was reversed by pretreatment with an alpha 2-adrenoceptor antagonist, idazoxan (5 mg/kg, i.p.). In rats which were catecholaminergically denervated with 6-hydroxydopamine, UK14,304 (10 microM) still inhibited the K(+)-evoked 5-HT release. Treatment with pertussis toxin (PTX) did not alter the K(+)-evoked release of 5-HT but abolished the inhibitory effect of UK14,304. These findings suggest that 5-HT release is functionally modulated via alpha 2-adrenoceptors located on the serotonergic nerve terminals in the rat hippocampus and furthermore, the possibility that the inhibitory of alpha 2-adrenoceptors is linked to G-proteins which are substrates of PTX.
Numazawa
R
R
Department of Anesthesiology, Hokkaido University School of Medicine, Sapporo, Japan.
Yoshioka
M
M
Matsumoto
M
M
Togashi
H
H
Kemmotsu
O
O
Saito
H
H
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D000068438:Brimonidine Tartrate; D004146:Dioxanes / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D037342:Pertussis Toxin; D011188:Potassium / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D004146:Dioxanes; D007093:Imidazoles; D011810:Quinoxalines; D010566:Virulence Factors, Bordetella; D012701:Serotonin; D013779:Tetrodotoxin; D000068438:Brimonidine Tartrate; D016627:Oxidopamine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D011188:Potassium; D019329:Idazoxan