Authors: Tsoi, C.; Swedmark, S.

Source: Current Drug Metabolism, Volume 6, Number 3, June 2005 , pp. 275-285(11)

Publisher: Bentham Science Publishers

Abstract:

Sulfation has been thoroughly studied in several species including e.g. man and rat. However, one important species often used for pharmacological drug studies is the dog. Here we describe recent advances as well as older data in the field of dog sulfation. Species differences in sulfation have been reported. Stereoselectivity, inhibition by pentachlorophenol, bioactivation of DNA binding species, and gender differences have also been observed for canine sulfotransferases (SULTs). Several drugs are being sulfated in vivo in dog, e.g. xamoterol, 4'-hydroxypropanolol, paracetamol and salicylamide. However, studies have shown that also e.g. canine hepatocytes and liverslices will sulfate substrates e.g. paracetamol and 7-hydroxycoumarin in in vitro experiments. Recently, three different enzymes have been cloned and characterized from canine liver, cSULT1A1, cSULT1B1 and cSULT1D1. cSULT1A1 being very similar to the human ortholog in terms of substrate specificity and is also ubiquitously expressed in canine tissues. The cSULT1B1 enzyme is also very similar in both distribution pattern as well as substrate preference compared to the human ortholog. The third enzyme, cSULT1D1, sulfates dopamine with high efficiency and it has no counterpart in man since it is found as a pseudogene. The importance of amino acid residue 247 in cSULT1D1 will be discussed since it can alter the ratio of sulfation of dopamine versus para-nitrophenol. In addition, the phenomenon of the high expression of the canine enzymes in colon is discussed.

Keywords: canine; sulfotransferase; csult a; csult b; csult d; hepatocytes; liverslices

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389200054021816

Affiliations: 1: Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden.

Publication date: 2005-06-01

More about this publication?

• Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:
  
  In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.

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