ORGANIC ANION TRANSPORT IN DOG TRACHEA

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Organic anion transport across epithelia is important in excretion of metabolites and in delivery of metabolic substrates, drugs, and transport modifiers to cells and strategic sites. In kidney, para-aminohippurate (PAH) is transported into the cell against an electrochemical gradient; this transport is inhibited by compounds of similar structure and by low K, ouabain and changes in pH. Little is known about organic anion transport in the lungs and airways which actively secrete Cl and absorb Na. This proposed research will characterize organic anion transport in the airways using Ussing chamber techniques and the dog trachea as a model of the airway epithelium. The specific aims are to (1) measure unidirectional fluxes of PAH and phenol red, prototype organic anions; (2) determine the driving forces for PAH and phenol red using tissue analysis and measurement of membrane potentials; (3) examine the role of inorganic ions including Na and HCO3 on this transport; and (4) examine the effects of known organic anion inhibitors on PAH and phenol red transport. Similar experiments using other organic anions of pharmacologic importance including cephalothin, tetracycline and benzylpenicillin will also be performed. Experimental manipulations of the tissues that will be used to describe the characteristics and reveal the mechanisms of PAH and phenol red transport include: (1) concentration dependence; (2) paracellular fluxes; (3) energy-dependence (removal of oxygen, addition of iodoacetate); (4) absence of Na transport (blocked by ouabain or Na-free bathing solutions; (5) absence of HCO3 transport (HCO3-free solutions; DIDS); and (6) presence of known organic anion inhibitors (probenecid; 2, 4, dinitrophenol; cephalothin).