Lipoxygenase product controls the regulatory volume decrease of human platelets.
SUMMARY. Blood platelets exposed to hypotonic medium are known to undergo a regulatory volume decrease (RVD), mediated by increased conductive permeability of K(+) and Cl(-). It is presently shown that RVD in platelets is controlled by a lipoxygenase product, apparently by a selective regulation of K(+) permeability. This conclusion is supported by the following observations: (a) lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA), N-(3-phenoxycinnamyl)-acetohydroxamic acid (BW A4C), methyl 2-[(3,4-dihydro-3,4-dioxo-naphthalenyl)amino]-benzoate (CGS 8515), and 5,8,11,14-eicosatetraynoic acid, inhibit RVD with IC(50) values of 3,6,10, and 5 μM, respectively. In contrast, aspirin and indomethacin, known cycloxygenase inhibitors, are innocuous; (b) an eluate from platelets undergoing RVD restores RVD in NDGA-treated platelets; (c) the eluate is unstable (t(1/2) = 8 s and 2 min in the presence and absence of platelets, respectively); furthermore, albumin promotes platelet RVD; (d) known lipoxygenase products, 12-hydroperoxyeicosatetraenoic acid, 12-hydroxyeicosatetraenoic acid and leukotriene D(4), restore RVD in NDGA-treated platelets at 0.1-1.0 μM; (e) the extended hypotonic swelling of gramicidin-treated platelets, expressing Cl(-) permeability, is insensitive to NDGA. It is hypothesized that the lipoxygenase product selectively opens K(+) channels in platelets, in analogy with the effect of lipoxygenase products in cardiac atrial cells and Aplysia sensory neurons.
Department of life Sciences (Biology), Ben-Gurion University, Beer-Sheva, Israel, 84105.
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Margalit
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Livne