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Agonist‐Induced Phosphoinositide Hydrolysis in Choroid Plexus
Author(s) -
Conn P. Jeffrey,
SandersBush Elaine
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.tb13085.x
Subject(s) - choroid plexus , inositol , inositol phosphate , endocrinology , medicine , histamine , agonist , chemistry , inositol trisphosphate , neurotransmitter , serotonin , receptor , pharmacology , biology , biochemistry , central nervous system
5‐Hydroxytryptamine (5‐HT, serotonin) stimulates phosphoinositide hydrolysis in choroid plexus by interacting with the 5‐HT lc site. In the present study, the effects of 5‐HT were compared with those of other agonists. 5‐HT stimulates a rapid release of all three inositol sugars in a mianserin‐sensitive manner. Inositol bisphosphate and inositol trisphosphate levels increase about twofold within 2.5 min, whereas inositol monophosphate levels are not appreciably elevated until 5 min. In contrast, glutamate, carbachol, histamine, substance P, and vasopressin, agents that increase phosphoinositide hydrolysis in other tissues, do not stimulate this response in choroid plexus. High concentrations of norepinephrine increase inositol phosphate release in choroid plexus, but this effect is apparently mediated by activation of the 5‐HT lc site. The depolarizing agents KCl and veratrine also fail to stimulate phosphoinositide hydrolysis in choroid plexus. These results, combined with the finding that the phosphoinositide response to 5‐HT is insensitive to tetrodotoxin, suggest that the effects of 5‐HT are not secondary to neurotransmitter release. Furthermore, an indirect effect mediated via arachidonic acid metabolism is unlikely, since inhibitors of cyclooxygenase and lipoxygenase do not reduce the 5‐HT response. We conclude, therefore, that phosphoinositide hydrolysis is the transducing mechanism of the 5‐HT 5‐HT lc receptor and that the choroid plexus will serve as a useful model system for studies of this receptor.