The work horses for detoxification are 1) MRP1, the transmembrane transporter serving most cells in the body for exporting toxins to circulation, 2) OATP
, the basolateral membrane transporter which moves toxin conjugates from the blood into the hepatocytes or renal tubule epithelial cells, and 3) MRP2, the apical transporter that moves toxin conjugates (and some bile salts) into the bile canaliculus or renal proximal tubule lumen.
Compared to other PET tracers developed to study liver transporters which are transported quite selectively by the OATPs
and MRP2 and BCRP [3,4] bile acid-based tracers such as [[sup.18]F] LCATD, [[sup.18]F]FCA and [[sup.11]C]Cholylsarcosine are generally handled by the same transporters involved in uptake and efflux of endogenous bile acids (NTCP, OATP1B1, OATP1B3, BSEP, and MRP2) [24-26], making them the best candidates to study physiology and pathophysiology of the hepatic bile acid transport in vivo [22,23,27].
Funk, "Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP
) substrates on OATP1B1, OATP2B1, and OATP1B3," Drug Metabolism & Disposition, vol.
Tamai, "Organic anion transporting polypeptide (OATP
)2B1 contributes to gastrointestinal toxicity of anticancer drug SN-38, active metabolite of irinotecan hydrochloride," Drug Metabolism and Disposition, vol.
Abbreviations are used as follows: organic cation transporter (OCT), organic anion transporter (OAT), organic anion transporting polypeptide (OATP
), [Na.sup.+]-taurocholate cotransporting polypeptide (NTCP), breast cancer resistance protein (BCRP), bile salt export pump (BSEP), multidrug resistance protein (MDR), multidrug resistance-associated protein (MRP), organic solute transporter (OST), and multidrug and toxin extrusion protein (MATE) .
Decreased systemic exposure to certain medications could occur through grapefruit's inhibition of organic anion-transporting polypeptides (OATPs
Kim, "Organic anion-transporting polypeptide (OATP
) transporter family and drug disposition," European Journal of Clinical Investigation, Supplement, vol.
Abbreviations LC-MS/MS: Liquid chromatography tandem mass spectrometry OATP
: Organic anion-transporting polypeptide P-gp: P-glycoprotein QC: Quality control SIL: Stable isotope label SILAC: Stable isotope labeling with amino acids in cell culture UW: University of Washington.
transporters play important roles in the cellular uptake of variety of endogenic and xenobiotic compounds in the intestine and liver (Klaassen and Aleksunes 2010).
Treatment with 1, 10, or 50 ng/mL IL-6, 20 ng/mL IL-1ra, 300 [micro]M oATP
, 200 [micro]M [La.sup.3+], 1:500 Cx[43.sup.(E2)] antibody or 200 [micro]M [sup.10]Panx1 was simultaneous to cytokine treatment.
10 mmol of salicylaldehyde, substituted salicylaldehydes (Sal), 2-hydroxyacetphenone (HAP), 2-hydroxypropiophenone (HPP) or 2-hydroxy-1-napthaldehyde (HNP) with 10 mmol of 2-aminothiophenol (OATP
) were taken in a round bottomed flask, containing 50 mL of ethanol, fitted with a reflux condenser and a silica gel guard tube.
To examine the performance of the improved iterative prediction model for multiple stop arrival times (IMATP), we have implemented work compared with a history mean prediction model (HMP), a single stop arrival time prediction model (OATP
) and an iterative multiple stop arrival time prediction model (MATP).