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In Vivo Determination of 5‐Hydroxytryptamine Receptor‐Stimulated Phosphoinositide Turnover in Rat Brain
Author(s) -
Hide Izumi,
Kato Tadahiro,
Yamawaki Shigeto
Publication year - 1989
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.1471-4159.1989.tb07369.x
Subject(s) - inositol , in vivo , inositol phosphate , ritanserin , receptor , chemistry , inositol trisphosphate , medicine , endocrinology , phosphatidylinositol , receptor antagonist , quipazine , antagonist , biology , serotonin , biochemistry , 5 ht receptor , signal transduction , microbiology and biotechnology
Phosphoinositide turnover stimulated by 5‐hy‐droxytryptamine (5‐HT) receptors in the intact rat brain was studied using an in vivo method. Phosphoinositides in the rat brain were prelabeled with [ 3 H]inositol injected into the lateral cerebral ventricles. The rats were killed by microwave irradiation after 48 h and the contents in the frontal cortex of 3 H‐inositol phosphates, [ 3 H]inositol‐1‐monophosphate ([ 3 H]IP 1 ), [ 3 H]inositol‐l,4‐bisphosphate ([ 3 H]IP 2 ), and a mixture of [ 3 H]inositol‐l,4,5‐trisphosphate and [ 3 H]inositol‐1,3,4‐trisphosphate ([ 3 H]IP 3 ) were assayed by HPLC. Lithium treatment (10 mEq/kg, i.p., 2 h before) increased the content of[ 3 H]IP 1 and[ 3 H]IP 2 . 5‐Methoxy‐ N ′, N ‐dimethyltryptamine (5‐MeODMT) and quipazine, 5‐HT agonists, significantly increased the amount of 3 H‐inositol phosphates under lithium pretreatment. The response to 5‐MeODMT was inhibited by ritanserin, a 5‐HT 2 antagonist, but not by (—)‐propranoloI, a 5‐HT 1 antagonist. These results suggest that phosphoinositide turnover in the rat frontal cortex in vivo is stimulated by 5‐HT 2 receptor activation. It is considered that this method will be useful for measurement of 5‐HT 2 receptor‐stimulated phosphoinositide turnover in vivo to examine the in vivo effects of various psychotropic drugs such as antidepressants.