Storage of biogenic amines in intact blood platelets of man. Dependence on a proton gradient.
The actions of ionophores with different ion specificities and of thrombin on the release of 14C-labeled 5-hydroxytryptamine, [3H]noradrenaline, and endogenous ATP were measured in human platelets suspended in media with various K+ and Na+ concentrations. Besides thrombin, those ionophores [monensin, nigericin, and the combination of carbonylcyanide-p-trifluoromethoxyphenyl hydrazone (FCCP) with nonactin and/or valinomycin] which cause a rapid collapse of H+ gradients induced a fast and virtually total release of 14C-labeled 5-hydroxytryptamine and [3H]noradrenaline into the various media. FCCP alone, which causes an inversion of the membrane potential to inside negative values, induced a considerably slower amine release. Changes in the K+ and Na+ gradients did not lead to amine release, nor did interference with energy transduction by antimycin A with or without glycolysis inhibitors. Monensin and FCCP did not release ATP, whereas thrombin, added before or after incubation of platelets with FCCP and monensin, caused a marked liberation of the nucleotide. It is concluded that in intact human platelets (a) the intragranular storage of 5-hydroxytryptamine and noradrenaline mainly depends on the proton gradient across the granular membrane, and (b) ionophores causing a collapse of H+ gradients induce non-exocytotic release of 5-hydroxytryptamine and noradrenaline from intracellular storage granules.
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000968:Antimycin A / Q000494:pharmacology; D001679:Biogenic Amines / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D018942:Macrolides; D008985:Monensin / Q000494:pharmacology; D009550:Nigericin / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium; D011522:Protons; D012701:Serotonin / Q000378:metabolism; D012964:Sodium
D000900:Anti-Bacterial Agents; D001679:Biogenic Amines; D018942:Macrolides; D011522:Protons; D012701:Serotonin; D000968:Antimycin A; D008985:Monensin; D012964:Sodium; D009550:Nigericin; D011188:Potassium; C050476:nonactin; D009638:Norepinephrine