Differential effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on various 5-HT receptor binding sites in the rat brain

doi:10.1016/0028-3908(94)90072-8

Neuropharmacology

Volume 33, Issues 3–4, March–April 1994, Pages 423-431

https://doi.org/10.1016/0028-3908(94)90072-8 Get rights and content

Abstract

The effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an alkylating agent producing irreversible blockade of various membrane bound receptors in brain, were investigated on four different types of serotonin receptors, 5-HT_1A, 5-HT_1B, 5-HT_2A and 5-HT₃, in various brain regions in the rat. In addition, the fate of central benzodiazepine- and “R”-zacopride-specific binding sites was also examined in rats treated with EEDQ. Membrane binding assays and/or quantitative autoradiography with appropriate radioligands indicated that EEDQ inactivated 5-HT_1A, 5-HT_1B and 5-HT_2A sites, but was poorly active on 5-HT₃, benzodiazepine and “R” sites. Among the receptors affected by EEDQ, hippocampal 5-HT_1A sites were the most sensitive to the alkylating agent (ID₅₀ ~ 1 mg/kg i.p.), followed by the cortical 5-HT_2A (ID₅₀ ~ 3 mg/kg i.p.) and the striatal 5-HT_1B (ID₅₀ ~ 6 mg/kg i.p.) sites. Pretreatment by selective ligands partially protected hippocampal 5-HT_1A sites from irreversible inactivation by EEDQ (10 mg/kg i.p.) with the following order of efficacy: WAY 100635 > spiperone > BMY 7378 > ipsapirone. Similarly, pretreatment by spiperone (5 mg/kg i.p.) also reduced the ability of EEDQ to inactivate cortical 5-HT_2A receptors. Analyses of the time-course recovery of respective binding sites after EEDQ administration showed that the turnover rate of 5-HT_1A sites did not significantly differ in the dorsal raphe nucleus and in various forebrain areas (hippocampus, septum, crebral cortex; half-life: ~4 days), but was lower than that of cortical 5-HT_2A sites (half-life: 2.9 days).

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^*: Present address: CNS Biological Research Department, American Cyanamid Co., Medical Research Division, Lederie Labs, Pearl River, NY 10965, U.S.A.

^†: Present address: Unitéde Pharmacologie Neuro-immuno-en-docrinienne, Institut Pasteur, 75724 Paris Cedex 15, France

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Differential effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on various 5-HT receptor binding sites in the rat brain

Abstract

Eur. J. Pharmac.

Biochem. Pharmac.

Biochem. Pharmac.

Neuroscience

Neurosci. Lett.

Neuropharmacology

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Life Sci.

FEBS Lett.

Biochem. Pharmac.

Trends Pharmac. Sci.

Eur. J. Pharmac.-Molec. Pharmac. Sect.

J. biol. Chem.

J. biol. Chem.

Eur. J. Pharmac.

Eur. J. Pharmac.

Neuropharmacology

Eur. J. Pharmac.

Brain Res.

Long term treatment with desipramine increases the turnover of α2-adrenoceptors in the rat brain

Molec. Pharmac.

In vitro and in vivo irreversible blockade of cortical S2 serotonin receptors by N-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline: a technique for investigating S2 serotonin receptor recovery

J. Neureichem.

Differential serotonin2 receptor recovery in mature and senescent rat brain after irreversible receptor modification: Effect of chronic reserpine treatment

J. Pharmac. exp. Ther.

Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus. I. Effect of spiperone

J. Pharmac. exp. Ther.

Identification of residues important for ligand binding to the human 5-hydroxytryptamine1A serotonin receptor

Molec. Pharmac.

Acetylcholine receptor turnover in membranes of developing muscle fibers

J. cell Biol.

Long term treatment with desipramine increases the turnover of α₂-adrenoceptors in the rat brain

Differential serotonin₂ receptor recovery in mature and senescent rat brain after irreversible receptor modification: Effect of chronic reserpine treatment

Differential properties of pre- and postsynaptic 5-hydroxytryptamine_1A receptors in the dorsal raphe and hippocampus. I. Effect of spiperone

Identification of residues important for ligand binding to the human 5-hydroxytryptamine_1A serotonin receptor