NITRIC-OXIDE INHIBITS ATP-DEPENDENT CA2-VESICLES( UPTAKE INTO PLATELET MEMBRANE)

The reduction by nitric oxide donors of Ca2+ mobilization in stimulate d platelets lend us to investigate the direct effect of authentic NO o n ATP-dependent Ca2+ uptake into platelet membrane vesicles. The effec ts of NO were compared to those of thapsigargin and 2,5-di-(t-butyl)-1 ,4-benzohydroquinone, two specific inhibitors of the sarco/endoplasmic reticulum Ca2+-ATPases. All three compounds modulated the initial rat e of ATP-dependent Ca2+ uptake. NO effects on the initial rate of acti ve Ca2+ uptake were biphasic, with an inhibition above 10 nmol/L and a stimulation below this concentration. These effects could not be attr ibuted to cGMP, its usual effector molecule, or to nitrite ions, its m etabolic product. NO inhibitory effects were decreased after a five mi n incubation, indicating that they were due to a short-lived compound and reversible. These results suggest that NO is functionally coupled to SERCA pumps of the dense tubular system through a cGMP-independent mechanism. (C) 1996 Academic Press, Inc.