Agonist-induced Ca2+ influx in human neutrophils is secondary to the emptying of intracellular calcium stores.
Emptying of the intracellular calcium stores of human neutrophils, by prolonged incubation in Ca(2+)-free medium, by treatment with low concentrations of the Ca2+ inophore ionomycin, or by activation with cell agonists, increased the plasma-membrane permeability to Ca2+ and Mn2+. The chemotactic peptide formylmethionyl-leucyl-phenylalanine and the natural agonists platelet-activating factor and leukotriene B4 released different amounts of calcium from the stores and induced Ca2+ (Mn2+) uptake, the rate of which correlated inversely with the amount of calcium left in the stores. The increased Mn2+ uptake induced by these agonists was persistent in cells incubated in Ca(2+)-free medium, but returned to basal levels in cells incubated in Ca(2+)-containing medium, with the same time course as the refilling of the calcium stores. The calcium-stores-regulated Mn2+ influx, including that induced by agonists, was prevented by cytochrome P-450 inhibitors. We propose that agonist-induced Ca2+ (Mn2+) influx in human neutrophils is secondary to the emptying of the intracellular stores which, in turn, activates plasma-membrane Ca2+ channels by a mechanism involving microsomal cytochrome P-450, similar to that described previously in thymocytes [Alvarez, Montero & Garcia-Sancho (1991) Biochem. J. 274, 193-197].
Montero
M
M
Departamento de Bioquímica, Biologia Molecular y Fisiologia, Facultad de Medicina, Universidad de Valladolid, Spain.
Alvarez
J
J
Garcia-Sancho
J
J
D002118:Calcium / Q000097:blood*; D004533:Egtazic Acid / Q000494:pharmacology*; D016257:Fura-2; D006801:Humans; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology*; D007700:Kinetics; D008345:Manganese / Q000097:blood; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*
D010972:Platelet Activating Factor; D008345:Manganese; D004533:Egtazic Acid; D015759:Ionomycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium; D016257:Fura-2