The dependence on Ca2+ of the guanine-nucleotide-activated polyphosphoinositide phosphodiesterase in neutrophil plasma membranes

Abstract

The requirement for Ca2+ for the activation of polyphosphoinositide phosphodiesterase was studied with the guanine nucleotide analogue guanosine 5''-[.gamma.-triphosphate (GTP.gamma.S). Levels of Ca2+ that pertain in unstimulated neutrophils (100 nM) are obligatory for the full expression of enzyme activity stimulated with GTP.gamma.S. Reduction of Ca2+ to 1 nM leads to inhibition. Increasing the level of Ca2+ from 100 nM to 1000 nM does not alter enzyme activity. Guanosine 5''[.beta.-thio]diphosphate (GDP.beta.S) does not stimulate the phosphodiestease but is an effective inhibitor of activation of GTP.gamma.S. Ca2+ in the millimolar range can also activate the phosphodiesterase alone and this is not inhibited by GDP.beta.S. It is also shown that Sr2+ in the millimolar range can stimulate enzyme activity similarly to Ca2+.