Inhibition by extracellular ATP of organic anion transport in the perfused rat liver

Abstract

The action of extracellular ATP on organic anion transport in the bivascularly perfused rat liver was investigated, using bromosulfophthalein as a model substance. Transport was measured by means of the multiple-indicator dilution technique. The action of portal 100 μM ATP presented the following characteristics: (a) inhibition of bromosulfophthalein single pass extraction; the inhibition degree decreased with increasing bromosulfophthalein doses; (b) diminution of the influx rate coefficients; (c) 86.7% decrease of the maximal activity of the saturable component for bromosulfophthalein transport, but 100% increase of the non-saturable component; (d) diminution of the bromosulfophthalein flow-limited distribution space; (e) no significant alteration of the rate coefficients for metabolic sequestration. The action of ATP on organic anion transport in the intact liver occurred at much lower concentrations (10×) than those previously reported for isolated hepatocytes. This reinforces the suggestion that inhibition of organic anion transport could be a physiologically relevant effect of extracellular ATP.