InsP3 and Ins(1,3,4,5)P4 act in synergy to stimulate influx of extracellular Ca2+ in Xenopus oocytes

DeLisle, S.; Pittet, Didier; Potter, B. V.; Lew, Daniel Pablo; Welsh, M. J.

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Title		InsP3 and Ins(1,3,4,5)P4 act in synergy to stimulate influx of extracellular Ca2+ in Xenopus oocytes
Authors		DeLisle, S. Pittet, Didier Potter, B. V. Lew, Daniel Pablo Welsh, M. J.
Published in		American Journal of Physiology. 1992, vol. 262, no. 6 Pt 1, p. C1456-1463
Abstract		To investigate the role of D-myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] in the regulation of Ca2+ influx, we injected inositol phosphates into Xenopus oocytes and measured Ca(2+)-gated Cl- current to assay intracellular free Ca2+ concentration ([Ca2+]i). To assess Ca2+ influx, we removed extracellular Ca2+ or added the inorganic Ca2+ channel blocker Mn2+ to the extracellular bath and measured the resulting change in Cl- current. Ins(1,3,4,5)P4 did not cause Ca2+ influx when injected alone or when preceded by an injection of Ca2+. In contrast, Ins(1,3,4,5)P4 stimulated Ca2+ influx when injected after the poorly metabolized inositol trisphosphate (InsP3) analogues D-myo-inositol 1,4,5-trisphosphorothioate [Ins(1,4,5)P3S3] or D-myo-inositol 2,4,5-trisphosphate [Ins(2,4,5)P3]. These results indicate that Ins(1,3,4,5)P4 is not sufficient to stimulate Ca2+ influx but acts in synergy with InsP3s to cause Ca2+ influx. We also studied the effect of Ca2+ influx on the immediate metabolism of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in single oocytes. Ca2+ influx shunted the metabolism of Ins(1,4,5)P3 toward the formation of Ins(1,3,4,5)P4 and away from D-myo-inositol 1,4-bisphosphate [Ins(1,4)P2]. These results suggest that there is a positive feedback regulatory mechanism in which Ca2+ influx stimulates Ins(1,3,4,5)P4 production and Ins(1,3,4,5)P4 stimulates further Ca2+ influx.
Keywords		Animals — Biological Transport/drug effects — Calcium/ metabolism — Chloride Channels — Chromatography, High Pressure Liquid — Drug Synergism — Female — Inositol 1,4,5-Trisphosphate/metabolism/ pharmacology — Inositol Phosphates/isolation & purification/metabolism/ pharmacology — Ion Channels/physiology — Kinetics — Manganese/pharmacology — Membrane Proteins/drug effects/physiology — Oocytes/drug effects/ metabolism — Time Factors — Xenopus laevis
Identifiers		PMID: 1377444
Full text		Article - Limited access to UNIGE Other version: http://ajpcell.physiology.org/cgi/reprint/262/6/C1456.pdf
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités
Research group		Staphylocoques dorés résistants à la méthicilline et hygiène hospitalière (330)
Citation (ISO format)		DELISLE, S. et al. InsP3 and Ins(1,3,4,5)P4 act in synergy to stimulate influx of extracellular Ca2+ in Xenopus oocytes. In: American Journal of Physiology, 1992, vol. 262, n° 6 Pt 1, p. C1456-1463. https://archive-ouverte.unige.ch/unige:7159