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In Vitro and In Vivo Irreversible Blockade of Cortical S 2 Serotonin Receptors by N‐Ethoxycarbonyl‐2‐Ethoxy‐1,2‐Dihydroquinoline: A Technique for Investigating S 2 Serotonin Receptor Recovery
Author(s) -
Battaglia George,
Norman Andrew B.,
Newton Patricia L.,
Creese Ian
Publication year - 1986
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1986.tb13008.x
Subject(s) - ketanserin , serotonin , receptor , 5 ht receptor , receptor antagonist , chemistry , pharmacology , in vivo , antagonist , medicine , endocrinology , biology , biochemistry , microbiology and biotechnology
N ‐Ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquin‐oline (EEDQ) treatment, both in vitro and in vivo, results in an irreversible blockade of cortical S 2 5‐hydroxytryp‐tamine (serotonin) receptors. Incubation of rat cortical homogenates with EEDQ in vitro results in a concentration‐dependent (EC 50 ∼5 μ.M) and time‐dependent decrease in the B max of [ 3 H]ketanserin‐labeled S 2 serotonin receptors. Extensive washing of the homogenate following in vitro or in vivo EEDQ treatment does not result in an increase in the amount of [ 3 H]ketanserin binding, indicating that EEDQ acts to modify irreversibly cortical S 2 serotonin receptors. That the modification of S 2 receptor binding by EEDQ occurs at the recognition site of the receptor is indicated by the finding that coincubation with the S 2 receptor antagonist ketanserin, but not the D 2 3,4‐dihydroxyphenylethylamine (dopamine) receptor antagonist domperidone, selectively protects against the irreversible blockade of S 2 serotonin receptors. Peripheral administration of EEDQ results in a dose‐dependent reduction in cortical S 2 serotonin receptors with maximal effects (∼90% reduction) observed following 10 mg/kg (i.p.). Seven days following peripheral administration of EEDQ there is a recovery of S 2 serotonin receptors back to 74% of the original receptor population. These data demonstrate that EEDQ in vitro and in vivo acts as an irreversible antagonist of S 2 serotonin receptors and that it can be used to investigate the recovery rate of these receptors.