The role of transporters on drug therapy
Abstract: Pharmacodynamical
studies showed that most drugs elicit their effects by acting on 3 kinds of
protein molecules known as receptors, enzymes or transporters. Although their
detail properties had not been explained for decades the roles of transporters
in drug kinetics and dynamics has been well understood, even have been applied
in the therapy. Transporters are classified into 2 major classes, the solute
carriers (SLC) and ATP-binding cassette (ABC) families. SLC transporters do not
possess ATP binding site property as those of ABC transporters. SLC
transporters consist of 3 SLC subfamilies i.e. organic cation transporters
(OCTs), organic anion transporters (OATs) and organic anion transporting
polypeptides (OATPs). In contrast, ABC transporters require ATP hydrolysis to
transport substrate across cell membrane. Human ABC-transporters consist of
ABCA1-13, ABCB1-11, ABCC1-12, ABCD1-4, ABCE1, ABCF1-3 and ABCG1-8 subfamily.
Although the originally funtion of transporter is to transport specific
physiological substrate such as nutrient, hormone, cytokines, neurotransmitters
and other physiological subtances across cell membrane the specificity is not
restricted to each substrate. Drugs and other xenobiotics which have structural
similarity to the physiological substrates are recognized and transported by
the related transporters. The competition of them on transporters therefore may
lead to the occurence of drug-drug interactions (DDI) or drug-physiological
substrate interaction in the drug-kinetics phase. Many transporters located in
the liver, intestinal and renal epithelial cell membranes involve in the
transport of endogenous substance or xenobiotics including drugs play important
roles as protective barrier. Since transporters also serve as the targets of
drug action it is understood that transporters play important role in the
pathogenesis of diseases as well as in the drug therapy of diseases.
Keywords: drug transporters –
solute carries – ATP-binding cassette – organic cation transporters – organic
anion transporting polypeptides
Author: Ngatidjan
Journal Code: jpkedokterangg150355
