Platelet secretion induced by divalent cation ionophores

Interrelations of Platelet Aggregation and Secretion

“…7 is independent of actual intermediates or second messengers, we have considered how the overall scheme might relate to intermediates that have been implicated in stimulusresponse coupling in platelets. There is some evidence for a central role for Ca2+ in regulation of platelet function (17)(18)(19)(20), so that activation may involve an intracellular Ca2+ flux. One line of evidence for a Ca2+ flux is the ability of the divalent cation ionophore to activate platelets (17)(18)(19), and the ability of A23187 to cause shape change and primary aggregation suggests that these processes may also involve Ca2 .…”

“…There is some evidence for a central role for Ca2+ in regulation of platelet function (17)(18)(19)(20), so that activation may involve an intracellular Ca2+ flux. One line of evidence for a Ca2+ flux is the ability of the divalent cation ionophore to activate platelets (17)(18)(19), and the ability of A23187 to cause shape change and primary aggregation suggests that these processes may also involve Ca2 . Since shape change and aggregation can be seen in the absence of secretion, this would involve Ca2+ in a different compartment or simply as a weaker flux, consistent with Holmsen's suggestion that graded Ca2+ fluxes lead to graded responses (21).…”

Studies on the ionophorous antibiotics. VIII. Effects of monovalent and divalent cation ionophores on blood platelets.

“…It has been postulated that the excitation-secretion coupling processes of intracellular calcium regulate general cellular function by interacting with cyclic nucleotides.6,7) The divalent cation ionophores lasalocid A and A23187, which render membranes permeable to calcium, have recently served as valuable tools for understanding molecular mechanism of cell activation systems.8,9,10) In human platelets, these antibiotics stimulate calcium uptake and/or induce redistribution of intracellular calcium, thereby inducing the secretion of serotonin and adenine nucleotides as well as aggregation. 11,12) In this paper, studying the effects of etheromycin and lysocellin, ionophores of characteristic cation selectivity, on calcium movement and serotonin secretion in rabbit blood platelets, we demonstrate results which provide some support for a hypothesis that the platelet secretion reaction might be triggered by the cytoplasmic calcium released from the intracellular pools. …”

“…11,12) In this paper, studying the effects of etheromycin and lysocellin, ionophores of characteristic cation selectivity, on calcium movement and serotonin secretion in rabbit blood platelets, we demonstrate results which provide some support for a hypothesis that the platelet secretion reaction might be triggered by the cytoplasmic calcium released from the intracellular pools. The association constants of the antibiotics for various cations or amines were determined in two-phase distribution experiments on the assumptions of 1: 1 complexes with monovalent cations and amines and 2: 1 complexes with divalent cations as described in the previous reports' Platelets were isolated by centrifuging the blood collected from normal male rabbits and washed twice, once with saline containing 1 mm EDTA and 25 mm Tris-maleate, pH 6.8 and once with saline buffered by 25 mm Tris-maleate, pH 6.8 and finally suspended in saline at a concentration of 2 109 platelets per ml.…”

Studies on the ionophorous antibiotics. XVI. The ionophore-mediated calcium transport and concomitant osmotic swelling of mitochondria.

“…[4][5][6] In mitochondria, these antibiotics cause depletion of intramitochondrial alkali and alkaline earth metal cations and induce a secondary release of anions, thereby inhibiting mitochondrial energy transducing reactions. '-9) These compounds, therefore, are considered to mimic naturally occurring cation/H+ antiport in the mitochondrial inner membrane and cause a net extrusion of cations.2,10) On the other hand, it is known that the neutral ionophores such as valinomycin and synthetic ligands, which form positively-charged complexes with cations, promote the electrophoretic influx of cations by mitochondria in response to electrical potential gradient on the inner membrane.11,12)…”