E B Berkhin1, M H Humphreys. 1. Division of Nephrology, San Francisco General Hospital, University of California San Francisco, San Francisco, California 94143, USA.
Abstract
BACKGROUND: Information on the molecular basis underlying organic anion and cation transport in renal tubules has expanded in recent years with the identification and characterization of numerous transporters. However, little is known about the regulation of this transport. METHODS: Both English and Russian language studies dealing with the regulation of organic ion transport by the kidney have been reviewed. RESULTS: This review summarizes the literature on the physiological and pharmacological aspects of the regulation of organic ion transport, linking this information where possible to underlying transport mechanisms. Current models of the tubular secretion of organic anions and cations are reviewed. Factors that inhibit or enhance tubular secretion of xenobiotics are described, and their influence on proximal tubule cell transport and function is discussed. Important roles for substrate stimulation, the adrenergic nervous system, numerous hormones, P-glycoprotein, and protein kinase C activity have been identified. CONCLUSIONS: Despite considerable advances in the understanding of basic transport pathways and mechanisms involved in the tubular secretion of organic compounds, there is still relatively little information on the regulation of this transport. Studies combining the techniques of integrative and cell physiology and molecular biology will provide significant new insights into the pathways regulating the tubular transport of these compounds.
BACKGROUND: Information on the molecular basis underlying organic anion and cation transport in renal tubules has expanded in recent years with the identification and characterization of numerous transporters. However, little is known about the regulation of this transport. METHODS: Both English and Russian language studies dealing with the regulation of organic ion transport by the kidney have been reviewed. RESULTS: This review summarizes the literature on the physiological and pharmacological aspects of the regulation of organic ion transport, linking this information where possible to underlying transport mechanisms. Current models of the tubular secretion of organic anions and cations are reviewed. Factors that inhibit or enhance tubular secretion of xenobiotics are described, and their influence on proximal tubule cell transport and function is discussed. Important roles for substrate stimulation, the adrenergic nervous system, numerous hormones, P-glycoprotein, and protein kinase C activity have been identified. CONCLUSIONS: Despite considerable advances in the understanding of basic transport pathways and mechanisms involved in the tubular secretion of organic compounds, there is still relatively little information on the regulation of this transport. Studies combining the techniques of integrative and cell physiology and molecular biology will provide significant new insights into the pathways regulating the tubular transport of these compounds.