Renal Membrane Transport Processes in Toxicology and Disease

摘要

Membrane transport processes play critical roles in numerous physiological and pharmacological processes, including maintenance of cellular ion gradients, regulation of metabolite distribution, drug accumulation in target organs, and drug excretion. For the kidneys, and in particular the proximal tubular cells, membrane transport processes are central to their roles in ion and metabolite homeostasis and drug distribution and metabolism. The kidneys are also frequent target organs for blood borne toxic chemicals. Key reasons for this are that the kidneys are exposed to chemicals in the blood because of the high rate of renal blood flow relative to kidney weight and the process of glomerular filtration, the kidneys can readily accumulate chemicals inthe blood often to concentrations far exceeding those in plasma because of the presence of numerous transport proteins on renal plasma membranes, and because bioactivation enzymes exist within renal epithelial cells, particularly those of the proximal tubule, that can metabolize many drugs and other chemicals to reactive, toxic forms.