Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Evidence for an R(+)-[(dihydroindenyl)oxy]alkanoic acid-sensitive K+/Cl- co-transporter in human platelets and its interaction with the Na+/K+/2Cl- co-transporter.(Portland Press on behalf of the Medical Research Society and the Biochemical Society, 1997) de Silva, H.A.; Aronson, J.K.The K+/Cl- co-transport system is activated by a number of interventions, such as cell swelling and stimulation with N-ethylmaleimide. It is specifically inhibited by R(+)-[(dihydroindenyl)oxy]alkanoic acid and requires the presence of K+ and Cl- on the same side of the cell membrane. This co-transporter has been studied extensively, mainly in erythrocytes of many species, in which it plays a key role in cell volume regulation. Here we present evidence that human platelets contain K+/Cl- co-transporters. 2. We have studied the efflux of 86Rb+ (a marker for K+) from 86Rb(+)-loaded human platelets, and have defined their response to stimulation by N-ethylmaleimide. 3. N-Ethylmaleimide (0.5 and 1 mmol/l) stimulated an increase in cumulative 86Rb+ efflux in a concentration-dependent manner. This efflux was inhibited by R(+)-[(dihydroindenyl)oxy]alkanoic acid (10 mumol/l) but was insensitive to bumetanide. It also required the presence of external Cl-. 4. These observations suggest that 86Rb+ efflux from the platelets stimulated by N-ethylmaleimide occurs via K+/Cl- co-transport. 5. When the K+/Cl- co-transporter was stimulated by N-ethylmaleimide we were unable to stimulate the Na+/K+/2Cl- co-transporter with a high external concentration of KCl or inhibit 86Rb+ efflux with bumetanide. Together with other evidence, this suggests that when the K+/Cl- co-transporter is stimulated with N-ethylmaleimide, the Na+/K+/2Cl- co-transporter is inhibited.Item Effects of high external concentrations of K+ on 86Rb+ efflux in human platelets: evidence for Na+/K+/2Cl- co-transport.(Portland Press on behalf of the Medical Research Society and the Biochemical Society, 1996) de Silva, H.A.; Carver, J.G.; Aronson, J.K.Na+/K+/2Cl- co-transport mediates a bidirectional symport of Na+, K+ and Cl-. The important properties of the co-transport system are its requirement for Na+, K+ and Cl- and its inhibition by loop diuretics such as bumetanide. This co-transporter has been described in a number of animal and human tissues. However, its presence in human platelets, although inferred, has not been demonstrated directly. 2. We have studied the efflux of 86Rb+ (a marker for K+) from Rb(+)-loaded platelets, and have defined their response to stimulation by high concentrations of external K+. 3. KCl (30-120 mmol/l) stimulated a concentration-dependent increase in 86Rb+ efflux from the platelets. This efflux was completely inhibited by bumetanide (10 mumol/l) but was insensitive to ouabain and R(+)-[(dihydroindenyl)oxy]alkanoic acid. It also required Cl- in the external medium, but did not depend on the presence of extracellular Na+. 4. These observations suggest that 86Rb+ efflux from platelets stimulated by external K+ occurs via Na+/K+/2Cl- co-transport acting in a K+/K+ (K+/Rb+) exchange mode. 5. Non-stimulated efflux of 86Rb+ from the platelets (i.e. in the presence of 5 mmol/l K+) had the characteristics of Na+/K+/2Cl- co-transport acting in normal mode.