Tran, Johan M.; Farrell, Melanie A.; Fanestil, Darrell D. published the artcile< Effect of ions on binding of the thiazide-type diuretic metolazone to kidney membrane>, Synthetic Route of 35564-86-4, the main research area is kidney metolazone sodium chloride transport.
The effect of a number of ions on the binding of the thiazide-type diuretic metolazone (MTZ) to rat renal cortical membranes was studied to elucidate the mechanism of NaCl transport in the kidney distal tubule. Among the cations tested, Na+ stimulated the binding up to 2.4-fold over control. The effective concentration of Na+ that produced half-maximal stimulation was 2-17 mM. Li+, K+, NH4+, Rb+, and Cs+ produced little stimulation of binding of MTZ. Several anions including Cl- inhibited binding. The inhibition of binding of MTZ by Cl- was enhanced by Na+ and Li+. Scatchard anal. revealed that 50 mM Na+ increased the affinity for binding of MTZ from a Kd = 3.56 nM to Kd = 1.32 nM. Chloride, in the presence of 50 mM Na+, competitively inhibited binding of MTZ by suppressing the affinity to Kd = 9.27 nM without changing the maximal number of binding sites (0.733 pmol/mg). A mechanism for the MTZ-sensitive NaCl transport is proposed, in which the transporter protein possesses a binding site for Na+ and a binding site for Cl-, which is also the binding site for MTZ. Na+ binds to its site and increases the affinity for Cl-/MTZ. The binding of Cl- to the transporter enables the import of Na+ and Cl- across the tubule membrane. MTZ, however, when present competes with Cl- for the binding site on the transporter and prevents the transport of Na+ and Cl-.
American Journal of Physiology published new progress about Biological cotransport. 35564-86-4 belongs to class alcohols-buliding-blocks, and the molecular formula is C7H18ClNO5, Synthetic Route of 35564-86-4.
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