Transporters, drug action

Apart from very few exceptions, the entries in the main text do not contain drug names in their titles. Instead, drugs that are commonly used all over the world are listed in the Appendix. Also included in the Appendix are four-extensive sections that contain tables listing proteins such as receptors, transporters or ion channels, which are of particular interest as drug targets or modulators of drug action. 

Abraham, M. H., Chadha, H. S., Applications of a solvation equation to drug transport properties, in Lipophilicity in Drug Action and Toxicology. Pliska, V., Testa, B.,... 

Pinocytosis is a type of endocytosis that is responsible for the transport of large molecules such as proteins and colloids. Some cell types (e.g., endothelial cells) employ this transport mechanism extensively, but its importance in drug action is uncertain. 

Mechanisms of drug action. To mediate a response the drug can bind to the desired therapeutic target or to other molecular targets such as G-protein-coupled receptors (GPCRs), ion channels, or transporters on the cell membrane, or to intracellular targets such as enzymes and nuclear hormone receptors. 

There is a diversity of opinion regarding definitions and benefits of pharmacogenetics and pharmacogenomics.1 3 For example, pharmacogenetics is often considered to be the study of inter-individual variations in DNA sequence related to drug absorption and disposition (pharmacokinetics, PK) or drug action (pharmacodynamics, PD). Polymorphic variation in the genes that encode the functions of transporters,... 

In this situation, cell lines are shown to be resistant to colchicine, doxorubicin, vinblastine, and actinomycin D. This syndrome is accompanied by an increase in measurable membrane glycoprotein (the P-170 or permeability glycoprotein). It is believed that this protein transports hydrophobic chemicals out of cells and thereby prevents drug action. Current efforts to inhibit this efferent transport protein are currently underway but, sadly, have to date been largely unsuccessful (i5). 

Since the enzyme that converts dopamine to norepinephrine (dopamine (3-hydroxylase) is located only within the vesicles, the transport of dopamine into the vesicle is an essential step in the synthesis of norepinephrine. This same transport system is essential for the storage of norepinephrine. There is a tendency for norepinephrine to leak from the vesicles into the cytosol. If norepinephrine remains in the cytosol, much of it will be destroyed by a mitochondrial enzyme, monoamine oxidase MAO). However, most of the norepinephrine that leaks out of the vesicle is rapidly returned to the storage vesicles by the same transport system that carries dopamine into the storage vesicles. It is important for a proper understanding of drug action to remember that this single transport system, called vesicular transport, is an essential element of both synthesis and storage of norepinephrine. 

Moreland DE. Effects of toxicants on electron transport and oxidative phosphorylation. In Hodgson E, Levi PE, eds. Introduction to Biochemical Toxicology. 2nd ed. New York Wiley Interscience, 2001. Pratt WB, Taylor P, eds. Principles of Drug Action. New York Churchill Livingstone, 1990. 

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