title: Maitotoxin induces phosphoinositide turnover and modulates glutamatergic and muscarinic cholinergic receptor function in cultured cerebellar neurons.
abstract: Maitotoxin (MTX) stimulated inositol phosphate (IP) formation in primary cultures of rat cerebellar granule cells. MTX-induced IP production was dependent on extracellular Ca2+ 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 Ca2+ entry blockers, such as nimodipine, nisoldipine, Co2+, and Mn2+. 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 IC50 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 S6b-induced responses. Thus, MTX elicited a marked Ca2(+)-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.
authors.affiliation: Unit of Molecular Neurobiology, National Institute of Mental Health, Bethesda, Maryland.
authors.forename: W W
authors.initials: WW
authors.lastname: Lin
authors.forename: C Y
authors.initials: CY
authors.lastname: Lee
authors.forename: T
authors.initials: T
authors.lastname: Yasumoto
authors.forename: D M
authors.initials: DM
authors.lastname: Chuang
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006868:Hydrolysis; D008387:Marine Toxins / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D035964:Oxocins; D010716:Phosphatidylinositols / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017470:Receptors, Glutamate; D011976:Receptors, Muscarinic / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D000095702:Polyether Toxins
chemical_list: D002217:Carbachol; D005971:Glutamates; D018698:Glutamic Acid; D008387:Marine Toxins; D035964:Oxocins; D010716:Phosphatidylinositols; D017470:Receptors, Glutamate; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; C020394:maitotoxin; D000095702:Polyether Toxins