Is IMP Accumulation in Platelets a Good Indicator for Increased Cytoplasmic Ca++?

Abstract

Reduction of [ATP] and accumulation of hypoxanthine occurs in platelets·when consumption exceeds resynthesis of ATP. The intermediate IMP accumulates transiently ([IMP]↑) to a very varying degree. Several findings indicate that [IMP] is controlled by cytoplasmic [Ca++]: (1) The transient nature of [IMP]↑ would follow the release and subsequent uptake of cytoplasmic Ca++, the latter resulting in a return to resting state. (2) Under certain conditions antimycin does not cause [IMP]↑, but in combination with fluoride, which itself may cause release of intracellular Ca++, [IMP]↑ is prolonged, suggesting that Ca++ uptake is energy-requiring. (3) Concomitant addition of antimycin, deoxyglucose and gluconolactone causes irreversible [IMP]↑, suggesting that a rapid fall in [ATP] causes leakage of Ca++-from intracellular sites. Irreversible (IMP]↑ is also seen with high [A23l87] when cytoplasmic [Ca++] is irreversibly enhanced. (4) Secretion induced by 2-propyl-3-dimethylamino-5,6-methylenedioxyindene is accompanied by [IMP]↑. Chlortetracycline inhibits secretion and abolishes [IMP]↑. (5) The conversion of IMP to inosine + hypoxanthine in platelet lysates is enhanced by EGTA + Mg++ and inhibited by Ca++. This indicates that Ca++ inhibits Mg++-dependents 5′-nucleotidase responsible for IMP↑ inosine, which may explain the proposed regulatory effect of cytoplasmic Ca++ on [IMP]↑ in platelets. Since no reliable direct method is known for monitoring Ca++-movements in platelets, [IMP]↑ may be a useful indicator for [Ca++] in platelet cytoplasm.