Dissociation of renal organic anion transport from renal lipid metabolism. I. Endogenous nonesterified fatty acids (NEFA) as determinants of transport.

The objective of this study was to evaluate the hypothesis that nonesterified fatty acids (NEFA) are endogenous inhibitors of renal organic anion transport and that changes in renal NEFA content could modulate renal organic anion transport capacity. The addition of 1 mM palmitate to a suspension of renal tubules produced a tissue NEFA content of 665 +/- 105 micrograms/g and a 40% decrease in the tissue-to-medium concentration ratio for p-aminohippurate. Penicillin pretreatment enhanced p-aminohippurate tissue-to-medium concentration ratio in a neonatal rabbit proximal tubule suspension but failed to alter renal NEFA content from a control of 46.4 +/- 2.6 micrograms/g. Penicillin treatment did, however, decrease renal triglyceride content and increased serum NEFA from 87.7 +/- 3.4 to 129 +/- 6.8 micrograms/ml. Fasting increased serum triglyceride and increased serum NEFA from 33.9 +/- 3.1 to 370 +/- 200 micrograms/ml. Fasting decreased p-aminohippurate transport capacity 42% from a control tissue-to-medium concentration ratio of 6.78 +/- 1.2 but did not alter renal NEFA from a control value of 65 +/- 15 micrograms/g. The data support the suggestion that penicillin treatment can alter lipid metabolism in vivo but fail to support the suggestion that altered renal organic anion transport is due to altered renal NEFA content and further suggest that NEFA can alter renal organic anion transport only at a supraphysiological concentration.