Effect of maitotoxin analogues on calcium influx and phosphoinositide breakdown in cultured cells

M. Murata, F. Gusovsky, M. Sasaki, A. Yokoyama, T. Yasumoto, J. W. Daly

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13 Citations (Scopus)

Abstract

M. Murata, F. Gusovsky, M. Sasaki, A. Yokoyama, T. Yasumoto and J. W. Daly. Effect of maitotoxin analogues on calcium influx and phosphoinositide breakdown in cultured cells. Toxicon 29, 1085-1096, 1991.-Maitotoxin (MTX) and the analogues, bis-desulfated-MTX (didesulfo-MTX), monodesulfated-MTX (monodesulfo-MTX), and hydrogenated-MTX (H-MTX) were examined on 45Ca2+ influx and phosphoinositide breakdown with hamster insulinoma HIT cells and rat glioma C6 cells. The activity of MTX was greatly reduced either by desulfation or by hydrogenation. Didesulfo-MTX weakly stimulated calcium influx in HIT cells, but had no stimulatory effect on either calcium influx or phosphoinositide breakdown in C6 cells. All the analogues inhibited MTX-induced calcium influx in either HIT or C6 cells. Didesulfo-MTX inhibited the calcium influx elicited by 3 ng/ml MTX in C6 cells with an ic50 of 7.0±0.7 ng/ml. The data suggest that the sulfate groups in MTX are important for stimulation of calcium influx and phosphoinositide breakdown, but are not essential for binding to a receptor-site on cell membranes. Although catalytic reduction of double bonds in MTX reduced activity by nearly 100-fold, a tritiated H-MTX still represents a potential radioligand for identification of MTX-binding sites.

Original languageEnglish
Pages (from-to)1085-1096
Number of pages12
JournalToxicon
Volume29
Issue number9
DOIs
Publication statusPublished - 1991

ASJC Scopus subject areas

  • Toxicology

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