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. 2001 Apr 1;355(Pt 1):139–143. doi: 10.1042/0264-6021:3550139

Control of Ca2+ influx in human neutrophils by inositol 1,4,5-trisphosphate (IP3) binding: differential effects of micro-injected IP3 receptor antagonists.

E V Davies-Cox 1, I Laffafian 1, M B Hallett 1
PMCID: PMC1221721  PMID: 11256958

Abstract

Neutrophils signal Ca2+ changes in response to occupancy of G-protein-linked receptors such as the formylated peptide receptor. This Ca2+ signal is composed of two parts, inositol 1,4,5-trisphosphate (IP3)-triggered release of Ca2+ from an intracellular store and Ca2+ influx. In order to probe the relationship between these events, cytosolic free Ca2+ changes in neutrophils were monitored after micro-injection of agents which inhibit IP3 binding. Micro-injection of heparin into neutrophils totally inhibited both formylmethionyl-leucylphenylalanine-induced Ca2+ release and the subsequent Ca2+ influx. This effect was not due to prior depletion of Ca2+ stores. Furthermore, micro-injection with anti-IP3-receptor antibody also inhibited Ca2+ release. However, anti-IP3-receptor antibody and another high-molecular-mass IP3-binding antagonist, heparin-albumin conjugate, failed to inhibit the accompanying Ca2+ influx. It was concluded that two IP3-binding sites exist in neutrophils: one accessible by both heparin and the high-molecular-mass inhibitors of IP3 binding and responsible for Ca2+ release, and another inaccessible to high-molecular-mass molecules and responsible for Ca2+ influx.

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Selected References

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