Activation-associated alterations in neutrophil pyridine nucleotide levels: a potential regulatory role for calcium and calmodulin.

The concentration of NADP + NADPH in resting human neutrophils has been measured to be 24.0 +/- 2.7 X 10(-18) mol/cell. Upon activation with opsonized zymosan A, phorbol myristic acetate or N-formylmethionyl-leucylphenylalanine, neutrophil NADP + NADPH pools increase to 80.5, 84.0, and 54.0 X 10(-18) mol/cell, respectively. These increases in pyridine nucleotide concentration are blocked by the addition of the calcium antagonist 8-(N,N-dimethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride, while calcium ionophore A23187, in the presence of calcium, will trigger the increase in the absence of other stimuli. Calmodulin antagonists trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide also inhibit stimulus-induced increases in the NADP + NADPH pool. These studies are interpreted as suggesting a role for calcium and calmodulin, and possibly protein kinase C in the regulation of pyridine nucleotide concentration in the activated neutrophil.