Addition of the ionophore monensin to mouse neuroblastoma-rat glioma hybrid NG108-15 cells leads to a 20 to 30-mV increase in the electrical potential across the plasma membrane as shown by direct intracellular recording techniques and by distribution studies with the lipophilic cation 13H-tetraphenylphosphoniumt (TPP+) [Lichtshtein, D., Kaback, H. R. & Blume, A. J. (1979) Proc. NatL Acad. Sci. USA 76, 650-6541.The effect is not observed with cells suspended in high K medium, is dependent upon the presence of Na+ externally, and the concentration of monensin that induces half-maximal stimulation of TPP+ accumulation is approximately 1 pM. The ionophore also causes rapid influx of Na+, a transient increase in intracellular pH, and a decrease in extracellular pH, all of which are consistent with the known ability of monensin to catalyze the transmembrane exchange of H+ for Na+. Although ouabain has no immediate effect on the membrane potential, the cardiac glycoside completely blocks the increase in TPP+ accumulation observed in the presence of monensin. Thus, the hyperpolarizing effect of monensin is mediated apparently by an increase in intracellular Na+ that acts to stimulate the electrogenic activity of the Na+,K+-ATPase. Because monensin stimulates TPP± accumulation in a number of other cultured cell lines in addition to NG10815, the techniques described may be of general use for studying the Na+,K+ pump and its regulation' in situ.The Na+,K+-activated ATPase (Na+,K+'pump) (ATP phosphohydrolase, EC 3.6.1.3) is present in the membranes of excitable (1) and nonexcitable (2-4) tissues and represents a major pathway for Na+ and K+ transport across the plasma membrane of eukaryotic cells. Moreover, hydrolysis of ATP by this membranous enzyme is often accompanied by the simultaneous movement of three equivalents of Na+ out and two equivalents of K+ into the cell. This inequality in ion movements confers an electrogenic activity to the enzyme. That is, its activity results in the net outward movement of a positive current, which may lead to the generation of a membrane potential (AI, interior negative).Although the resting Az in nerve is due primarily to a K+ diffusion gradient ([K+Iin > [K+Iout), electrogenic Na+,K+-ATPase activity makes a contribution to A+I in certain cells (5, 6). Moreover, enhanced activity of the pump may have important consequences, because hyperpolarization will result. Presynaptically, this will lead to reduced transmitter release and postsynaptically, to decreased sensitivity to excitatory synaptic stimulation.Evidence has been presented indicating that the activity (7, 8) and coupling ratio-i.e., Na+ efflux/K+ influx (9, 10)-of the Na+,K+-ATPase are not constant, but are subject to regulation. In liver cells, for example, catecholamines, prostaglandin E1, and glucagon inhibit the Na+,K+ pump in a manner that is blocked by insulin, and these effects are related to changes in the intracellular concentration of cyclic AMP (11-13). In contrast, in frog skeletal muscle (14), rat s...
Isolutrol is the active principle isolated from aqueous tissue extracts of deep sea shark liver and gall-bladder. A previous study has demonstrated the ability of isolutrol to reduce hyperseborrhoea, which provides a rationale for its use in the treatment of acne. We have performed a double-blind clinical trial on 70 patients to evaluate the efficacy and skin tolerance of isolutrol 0.15 g/100 mL (Ketsugo) in the treatment of mild to moderate acne when compared with 5% benzoyl peroxide lotion. The results from this study showed that both isolutrol and benzoyl peroxide significantly improved patients' acne by reducing the number of inflamed lesions. Isolutrol did not significantly reduce the numbers of non-inflamed lesions whereas benzoyl peroxide did. Fewer side effects were experienced by patients treated with isolutrol when compared with benzoyl peroxide. These results indicate that isolutrol may be a useful adjunct in the treatment of acne, particularly in patients with inflamed lesions.
Retinoids provide some protection against ultraviolet radiation-induced skin damage. We have previously shown that topical all-trans retinoic acid prevents ultraviolet light from reducing the density of epidermal Langerhans cells in the epidermis but does not inhibit the development of immunosuppression to a locally applied contact sensitizer. We therefore investigated the ability of all-trans retinoic acid to modulate Langerhans cell induction of allogeneic T-cell proliferation in the mixed epidermal cell lymphocyte reaction. Langerhans cells isolated from all-trans retinoic acid-treated mice induced an enhanced mixed epidermal cell lymphocyte reaction. This is similar to Langerhans cells cultured with granulocyte-macrophage colony stimulating factor. Retinoic acid treatment also enhanced the allogeneic cell-stimulating capability of Langerhans cells isolated from ultraviolet-irradiated mice. Langerhans cells from all-trans retinoic acid-treated, ultraviolet-irradiated mice which were "matured" by 3 days in culture induced a larger mixed epidermal cell lymphocyte reaction than mice treated with solvent and ultraviolet irradiation. Thus all-trans retinoic acid treatment of mice causes Langerhans cell maturation and inhibits ultraviolet light from reducing their density or impairing their allogeneic cell-stimulating capacity. However, these mice remained immunosuppressed upon application of a contact sensitizer to irradiated or unirradiated skin. It is thus likely that, whereas all-trans retinoic acid protects local Langerhans cell numbers and function, it does not inhibit the production of an ultraviolet radiation-induced photoproduct which causes immunosuppression.
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