Oral and intravenous pharmacokinetics of taurine in sprague-dawley rats:the influence of dose and the possible involvement of the proton-coupled amino acid transporter, PAT1, in oral taurine absorption

摘要

Taurine is involved in various physiological processes, and one of the mostabundant amino acids in human. The aim was to investigate the mechanismfor intestinal absorption of taurine in vivo using also in vitro mechanisticstudies. Taurine absorption was measured in male Sprague-Dawley rats at10–997 mg/kg and 1–30 mg/kg for oral and intravenous administration,respectively. Oral absorption was measured in the presence of substrates forthe proton-coupled amino acid transporter, PAT1, that is, 200 mg/kg proline(Pro) and sarcosine (Sar), and in the presence of 2-Amino-2-norbornanecarboxylicacid (BCH) (200 mg/kg). BCH is not an inhibitor of PAT1 or the taurinetransporter, TauT, hence it was included as a negative control. In vitrostudies investigating the transport mechanism of taurine were conducted inhuman intestinal Caco-2 cells. The pharmacokinetic investigations showedthat intestinal taurine absorption was not saturable at the investigated doses,but that the time (tmax) to reach the maximal plasma concentration (Cmax)increased with dose. Furthermore, Sar and Pro, but not BCH, decreased taurineCmax. In vitro it was clearly shown that PAT1 mediated the cellularuptake of taurine and thereby facilitated the transepithelial taurine transport,which could be inhibited by Pro and Sar, but not BCH. In vivo and in vitroresults suggest that taurine absorption from the intestine is caused by PAT1.