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Lithium Selectively Inhibits Muscarinic Receptor‐Stimulated Inositol Tetrakisphosphate Accumulation in Mouse Cerebral Cortex Slices
Author(s) -
Whitworth P.,
Kendall D. A.
Publication year - 1988
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.1471-4159.1988.tb04865.x
Subject(s) - carbachol , inositol phosphate , inositol , muscarinic acetylcholine receptor , endocrinology , medicine , agonist , histamine , chemistry , stimulation , muscarinic agonist , inositol trisphosphate , receptor , cholinergic , mechanism of action , oxotremorine , cerebral cortex , biology , in vitro , biochemistry
The in vitro effects of Li on agonist‐ and depolarization‐stimulated accumulation of inositol phosphates were determined in mouse cerebral cortex slices. Of the agents examined, only the cholinergic agonist carbachol produced a significant accumulation of inositol tetrakisphosphate (InsP 4 ) in the absence of Li. Lithium at 5 m M enhanced the accumulation of inositol monophosphate (InsP 1 ) and inositol bisphosphate (InsP 2 ) due to all the stimuli used and potentiated inositol trisphosphate (InsP 3 ) accumulation due to histamine and noradrenaline, although at lower Li concentrations, carbachol‐stimulated InsP 3 accumulation was reduced. Li also enhanced InsP 4 accumulation in the presence of noradrenaline, histamine, and elevated KG level but, in marked contrast, reduced carbachol‐stimulated InsP 4 accumulation with an IC 50 of 100 μ M . There was a significant time delay between the initiation of carbachol stimulation and the beginning of the InsP 4 inhibition due to Li. The phorbol ester 4β‐phorbol 12β‐myristate 13α‐acetate did not mimic the effects of Li. The results suggest that muscarinic receptor‐mediated InsP 4 production might be one of the targets for the therapeutic action of Li.