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

• Published in: European journal of pharmacology Vol. 454; no. 2; pp. 225 - 234
• Main Authors: Fernandes, Talma R.L, de Oliveira, Denise S, Suzuki-Kemmelmeier, Fumie, Bracht, Adelar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-11-2002
• Subjects: Adenosine Triphosphate - pharmacology; Animals; ATP; Biological Transport - drug effects; Biological Transport - physiology; Dose-Response Relationship, Drug; Extracellular Space - drug effects; Extracellular Space - metabolism; Indicator-dilution experiment; Liver - drug effects; Liver - metabolism; Male; Organic anion transport; Organic Anion Transporters, ATP-Dependent - antagonists & inhibitors; Organic Anion Transporters, ATP-Dependent - metabolism; Perfused rat liver; Perfusion - methods; Rats; Rats, Wistar; Sulfobromophthalein - metabolism; Organic anion transport; ATP; Perfused rat liver; Indicator-dilution experiment
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)02488-3

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.