The effect of tienilic acid on Na+ and K+ transport in human red cells.
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Biomedical subjects
Publications and source records attributed to R Garay.
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1. Human red blood cells (R.B.C.) were incubated with phosphatidylcholine vesicles to obtain partial depletion of their membrane cholesterol. The kinetic parameters of the Na pump (affinities and maximal fluxes) were determined in these cells and compared with controls. 2. In the presence of internal K, progressive cholesterol depletion induces gradually (i) an increase of the maximal flux (ii) a reduction of the apparent affinity for internal Na. 3. In the absence of internal K, cholesterol depletion has no apparent effect, indicating that the observed changes were mediated by the internal K. Cholesterol depletion acts by increasing these two K effects: (i) activation of the maximal fluxes, and (ii) reduction of the internal Na affinity. 4. The cholesterol effect (on the K-pump interaction) is specific; it occurs without any change (i) in the affinities for internal Na and inorganic phosphate and for external Na and K, and (ii) in the number of pumping sites. 5. Under physiological conditions, cholesterol reduces the cation translocation rate and increases the selectivity of the pump for internal Na.
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We show that cancerisation presents some similarities with first order phase transitions. We analyze the barrier opposed by cytoxic cells against the proliferation of cancer cells.
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Recent studies in essential hypertensive patients and rats with genetic hypertension strongly suggested that the development of primary hypertension takes place by a transient and chronic "cascade" of events (i) excess Na+ intake, (ii) secretion of natriuretic factors, (iii) abnormal cells Na+ homeostasis in the vascular wall, due to the presence of inherited abnormalities in different Na+ transport systems, and (iv) increase in cytosolic free Ca2+ content and catecholamines. Canrenone, an antihypertensive drug, behaves like a partial agonist at the digitalis-receptor site of the Na+, K+ pump. We observed here that (i) a 4 hr preincubation of human red cells with this compound increases its antagonistic properties against ouabain, (ii) in cultured smooth muscle cells, canrenone counterbalances the increase in cytosolic free Ca2+ induced by ouabain, and (iii) in a model of experimental hypertension with increased endogenous "ouabain-like" factors (rats with reduced renal mass), the administration of canrenone tends to normalize Na+, K+-pump activity and decrease blood pressure.