Portal de Periódicos da CAPES

Influence of authentic nitric oxide on basal cytosolic [Ca 2+ ] and Ca 2+ release from internal stores in human platelets

1996; Wiley; Volume: 119; Issue: 7 Linguagem: Inglês

10.1111/j.1476-5381.1996.tb16047.x

1476-5381

Kim‐Hanh Le Quan Sang, Frédérique Lantoine, Marie‐Aude Devynck,

Antiplatelet Therapy and Cardiovascular Diseases

Nitric oxide (NO) donors inhibit platelet function and Ca 2+ mobilization evoked by different agonists. This led us to investigate the direct effects of authentic NO on basal cytosolic Ca 2+ concentration ([Ca 2+ ] i ) and on Ca 2+ mobilization induced by thrombin or by two inhibitors of intracellular Ca 2+ ‐ATPases, thapsigargin and 2,5‐di‐(t‐butyl)‐l,4‐benzohydroquinone (t‐BuBHQ). Cytosolic Ca 2+ concentration was evaluated with Fura‐2, in the absence of Ca 2+ influx. Addition of 5 μ m NO increased by 48% the basal cytosolic [Ca 2+ ] of resting human platelets whereas a lower concentration (0.1 μ m ) did not induce significant modifications. This NO‐induced Ca 2+ increase was inversely correlated with the basal level of cytosolic [Ca 2+ ]. NO pretreatment for 30 to 120 s decreased by 42 to 57% the transient [Ca 2+ ] i peak evoked by 0.10 u ml −1 thrombin and strongly attenuated the initial rate of [Ca 2+ ] i rise induced by 1 μ m thapsigargin or by 20 μ m t‐BuBHQ. The two components of the thapsigargin response, the Ca 2+ release due to inhibition of Ca 2+ pumps and the thromboxane A 2 ‐dependent self‐amplification mechanism, were inhibited by NO. The observation that a subsequent stimulation was still capable of eliciting Ca 2+ release suggests the presence of NO‐insensitive Ca 2+ stores. These findings indicate that nitric oxide can modulate basal cytosolic [Ca 2+ ] in unstimulated human platelets and decrease the Ca 2+ mobilization from NO‐sensitive internal stores evoked by stimulation of receptors or by Ca 2+ ‐ATPase inhibitors. This underlines the important role of nitric oxide in the modulation of platelet Ca 2+ handling.