Further observations on the uptake and effects of phosphonates in perfused rat liver studied by 31P-NMR

✍ Scribed by Koenraad Bruynseels; Paul Van Hecke; Florent Vanstapel

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 152 KB
• Volume: 12
• Category: Article
• ISSN: 0952-3480
• DOI: 10.1002/(sici)1099-1492(199908)12:5<275::aid-nbm567>3.0.co;2-s

✦ Synopsis

We examined the route of uptake of 2-aminoethylphosphonate (NEthPo) and of phenylphosphonate (PhePo; 10 mM each) in perfused liver by 31 P-NMR. Uptake of NEthPo was concentrative. The rate of uptake was reduced to 21 AE 2% (n = 3; all percentages refer to control rates) by substituting choline for Na , and to 21 AE 4% (n = 3), 32 AE 6% (n = 5) and 70 AE 5% (n = 3) by replacing Cl À by gluconate, SO 4 2À or NO 3

À

, respectively. Taurine (20 mM) reduced NEthPo uptake to 38 AE 6% (n = 3). The data are consistent with uptake of NEthPo by the Nacoupled Cl À -dependent b-amino acid transporter. A small fraction of NEthPo was incorporated into phospholipid. PhePo uptake evolved over 1 h towards levels of the membrane-permeant volume marker dimethyl methylphosphonate. Uptake depended on H , and was inhibited by 4,4'-diisothiocyanato-stilbene-2,2'-disulphonic acid (100 mM), bumetanide and furosemide (1 mM each) and a-cyano-4-OH-cinnamic acid (5 mM) to 31 AE 4% (n = 4), 28 AE 4% (n = 4), 27 AE 5% (n = 6) and 40 AE 7% (n = 4), respectively. These characteristics of PhePo uptake are reminiscent of H -coupled monocarboxylate transport. The monocarboxylates, lactate and acetate (20 mM), and the substrate analogue, phenylalanine (20 mM), were not inhibitory, while benzoic acid (20 mM) slightly inhibited (to 82 AE 5%; n = 4) PhePo uptake. The tested phosphonates (10 mM) did not significantly affect hepatic extraction of [ 3 H]-cholate or [ 3 H]-taurocholate (25 mM each; 1:3 bile salt:albumin). The monocarboxylate analogue, PhePo (10 mM), did not significantly interfere with disposal of lactate (0.3-5 mM).