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Maitotoxin Induces Phosphoinositide Turnover and Modulates Glutamatergic and Muscarinic Cholinergic Receptor Function in Cultured Cerebellar Neurons
Author(s) -
Lin WanWan,
Lee Chen Yuan,
Yasumoto Takeshi,
Chuang DeMaw
Publication year - 1990
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.1471-4159.1990.tb04939.x
Subject(s) - carbachol , pertussis toxin , glutamate receptor , muscarinic acetylcholine receptor , inositol phosphate , endocrinology , chemistry , medicine , histamine , oxotremorine , stimulation , cholinergic , biology , receptor , inositol , biochemistry , g protein
Maitotoxin (MTX) stimulated inositol phosphate (IP) formation in primary cultures of rat cerebellar granule cells. MTX‐induced IP production was dependent on extracellular Ca 2+ but independent of extracellular Na + . The stimulation of IP formation elicited by MTX was unaffected by pretreatment of cells with phorbol dibutyrate. pertussis toxin, and a variety of Ca 2+ entry blockers, such as nimodipine, nisoldipine, Co 2+ , and Mn 2+ . The presence of MTX markedly attenuated IP production induced by carbachol and glutamate, with no apparent effect on the responses to norepinephrine (NE), histamine, 5‐hydroxytryptamine (5‐HT), and endothelin‐1. The inhibition of the carbachol‐ and glutamate‐induced responses by MTX was dose dependent with IC 50 values of 1.2 and 0.5 ng/ml, respectively. Pretreatment of cells with a lower concentration of MTX (0.3 ng/ml) also attenuated carbachol‐ and glutamate‐induced IP formation, in a time‐dependent manner, with a decrease observed after 30 min prestimulation, but failed to affect NE‐, histamine‐, 5‐HT‐, endothelin‐1, and sarafotoxin S 6b ‐induced responses. Thus, MTX elicited a marked Ca 2+ ‐dependent phosphoinositide (PI) turnover in cerebellar granule cells and selectively inhibited carbachol‐ and glutamate‐induced PI hydrolysis. Possible mechanisms underlying these selective modulations are discussed.