5-HT-moduline, a 5-HT1B/1D receptor endogenous modulator, interacts with dopamine release measured in vivo by microdialysis

被引:21
作者
Bentué-Ferrer, D
Reymann, JM
Rousselle, JC
Massot, O
Bourin, M
Allain, H
Fillion, G
机构
[1] Fac Med, Pharmacol Lab, F-35043 Rennes, France
[2] Inst Pasteur, Unite Pharmacol Neuroimmunoendocrinienne, F-75724 Paris 15, France
[3] Fac Med, GIS Med, Pharmacol Lab, F-44035 Nantes, France
关键词
5-HT-moduline; 5-HT; (5-hydroxytryptamine; serotonin); dopamine; CP-93,129; microdialysis;
D O I
10.1016/S0014-2999(98)00586-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
5-Hydroxytryptamine-moduline (5-HT-moduline) is an endogenous tetrapeptide (Leu-Ser-Ala-Leu) recently isolated and characterized from mammalian brain. This compound interacts with 5-HT1B receptors as a non-competitive, high-affinity antagonist and has the properties of an allosteric modulator. 5-HT-moduline could play an important role in the regulation of serotonergic transmission and also, through heteroreceptors, dopaminergic transmission. The aim of this work was to examine the potential ability of 5-HT-moduline to modify the basal extracellular concentration of dopamine and its metabolites (3-methoxytyramine, dihydroxyphenylacetic acid and homovanillic acid), in the rat striatum and to determine its potential interaction with the stimulating activity of a specific 5-HT1B receptor agonist, 3-(1,2,5,6-tetrahydropyrid-4-yl) pyrrolo [3,2-b] pyrid-5-one (CP-93,129), on the release of dopamine. The technique is based on in vivo microdialysis using probes implanted in the striatum of the conscious rat. Results showed that the perfusion of 5-HT-moduline directly into this structure (1.25 mM) increased the striatal level of dopamine by two-fold (104% of the absolute basal release values, P = 0.0015) and that of 3-methoxytyramine by 3-fold (293%, P = 0.0001) without any change in the terminal metabolite concentrations. The intrastriatal administration of CP-93,129 induced a statistically significant, dose-dependent increase of dopamine levels (P < 0.0001). Coperfusion of 5-HT-moduline did not significantly alter the effect of CP-93,129 at 0.1 and 0.5 mM, but appeared to have an additive effect on the lowest dose (P = 0.0406). The results obtained show that 5-HT-moduline directly administered into the striatum increases the release of dopamine in this area. Presumably, this effect results from the desensitization of 5-HT1B receptors located on dopamine terminals. However, the fact that a 5-HT1B receptor agonist (CP-93,129) also increased the release of dopamine in the striatum and that 5-HT-moduline exhibited a slight additive effect with that of a low concentration of CP-93,129 suggests that the two substances interact with different mechanisms. (C) 1998 Elsevier Science B.V. All rights reserved.
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页码:129 / 137
页数:9
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