L-type amino acid transporters in two intestinal epithelial cell lines function as exchangers with neutral amino acids.

The present study examined the functional characteristics of the inward [(14)C]-L-leucine transporter in two intestinal epithelial cell lines (human Caco-2 and rat IEC-6). The uptake of [(14)C]-L-leucine was largely promoted through an energy-dependent and sodium-insensitive transporter, although a minor component of [(14)C]-L-leucine uptake ( approximately 15%) required extracellular sodium. [(14)C] -L-leucine uptake was insensitive to N-(methylamino)-isobutyric acid, but competitively inhibited by 2-aminobicyclo(2,2,1)-heptane-2-carboxylic acid (BCH).

The renal dopaminergic system, neurohumoral activation, and sodium handling in heart failure.

Background: Dopamine of renal origin exerts natriuretic and diuretic actions by activating specific receptors located in the renal proximal tubular epithelial cells. Heart failure (HF) is accompanied by activation of several neurohumoral systems. The interaction of these systems with the renal dopaminergic system and its effect on sodium handling in HF are not clarified.

Synthesis of 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and derivatives as potent and long-acting peripheral inhibitors of catechol-O-methyltransferase.

A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone) was found to exhibit the most potent and selective inhibition of peripheral COMT, with an inhibition profile more similar to entacapone 2 than tolcapone 1 (an equipotent peripheral and central inhibitor) but with much improved duration of action (7b, 70% inhibition and 2, 25% inhibition at 9 h after administration).