5-HT1B receptors modulate release of [3H]dopamine from rat striatal synaptosomes |
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Authors: | Hala Sarhan Isabelle Cloëz-Tayarani Olivier Massot Marie-Paule Fillion G Fillion |
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Institution: | (1) Unité de Pharmacologie Neuro-Immuno-Endocrinienne, Institut Pasteur, 28 rue du Dr. Roux, F-75724 Paris cedex, France e-mail: gfillion@pasteur.fr, Fax: +33-1-40613154, FR |
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Abstract: | The effect of the selective r5-HT1B agonist 3-(1,2,5,6-tetrahydro)-4-pyridil-5-pyrrolo 3,2-b] pyril-5-one (CP93,129) on the K+-evoked overflow of 3H]dopamine was studied in rat striatal synaptosomes loaded with 3H]dopamine. The aim of the study was to investigate the participation of 5-HT1B receptors in the serotonergic modulation of striatal dopaminergic transmission. The Ca2+-dependent, tetrodotoxin-resistant K+-evoked overflow of 3H]dopamine was inhibited by CP93,129 (0.01–100 μM) in a concentration-dependent manner (IC50=1.8 μM; maximal inhibition by 35.5% of control). ±]8-OH-DPAT, a 5-HT1A receptor agonist, +/–]DOI, a 5-HT2 receptor agonist, and 2-methyl-5-hydroxytryptamine, a 5-HT3 receptor agonist, at concentrations ranging from 0.01 μM to 100 μM did not show any significant effect. Neither ketanserin
(1 μM and 5 μM), a selective 5-HT2/5-HT1D receptor antagonist, nor ondansetron (1 μM), a 5-HT3 receptor antagonist, changed the inhibitory effect of CP93,129. SB224289, GR55562, GR127935, isamoltane and metergoline, selective
and non-selective 5-HT1B receptor antagonists, in contrast, used at a concentration of 1 μM, antagonized the inhibitory effect of CP93,129 (3 μM and
10 μM). SB224289, a selective 5-HT1B receptor antagonist, inhibited the effect of CP93,129 in a concentration-dependent manner; the calculated K
i value was 1.8 nM. Our results indicate that in rat striatal axon terminals the K+-evoked release of dopamine is regulated by the presynaptic 5-HT1B heteroreceptors. |
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Keywords: | Rat striatum CP93 129 5-HT1B receptors Serotonin [3H]dopamine release Synaptosomes |
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