Inhibitory presynaptic 5-hydroxytryptamine(2A) receptors regulate evoked glutamate release from rat cerebellar mossy fibers.

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Marcoli M, Rosu C, Bonfanti A, Raiteri M, Maura G

Inhibitory presynaptic 5-hydroxytryptamine(2A) receptors regulate evoked glutamate release from rat cerebellar mossy fibers.

J Pharmacol Exp Ther. 2001 Dec;299(3):1106-11.

PubMed ID

11714900 [ View in PubMed

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Abstract

We studied the pharmacological characterization of the 5-hydroxytryptamine(2) (5-HT(2)) heteroreceptor located on glutamatergic cerebellar mossy fiber nerve terminals. Depolarization-evoked overflow of endogenous glutamate from rat cerebellar "giant" mossy fiber synaptosomes was inhibited by 5-HT or (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)-DOI], exhibiting pD(2) (= -log EC(50)) values of 7.37 and 7.29, respectively. Trazodone inhibited the depolarization-evoked glutamate overflow, exhibiting lower potency (pD(2) = 6.42) and lower efficacy with respect to 5-HT or (+/-)-DOI (maximal inhibition, 54%, compared with 70% for either 5-HT or (+/-)-DOI). Ketanserin, a 5-HT(2A)/5-HT(2C) receptor antagonist, counteracted the inhibitory effect of (+/-)-DOI or trazodone. Inhibition of glutamate overflow by 5-HT, (+/-)-DOI, or trazodone was prevented by the selective 5-HT(2A) receptor antagonist R-(+)-alpha-(2,3-dimethyoxyphenyl)-1-(2-(4-fluorophenyl)ethyl)-4-piperidine-metha nol (MDL 100907), while the potent and selective 5-HT(2C) receptor antagonist 6-chloro-5-methyl-1-[6-(methylpyridin-3-yloxy)pyridin-3yl-carbamoyl] indoline (SB 242084) was ineffective. In cerebellar slices, MDL 100907 increased on its own the K(+)-evoked release of glutamate. It is concluded that the evoked release of glutamate from cerebellar mossy fibers can be controlled by inhibitory presynaptic 5-HT(2A) heteroreceptors, the receptors can be activated by endogenously released 5-HT, and trazodone behaves as a partial agonist at these receptors.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Trazodone	5-hydroxytryptamine receptor 2A	Protein	Humans	Yes	Antagonist	Details