MACROMOLECULAR
NATURE OF DRUG RECEPTORS
Most
receptors are proteins, presumably because the structures of polypeptides
provide both the necessary diversity and the necessary specificity of shape
and electrical charge. Receptors vary greatly in structure and can be
identified in many ways. Traditionally, drug binding was used to identify or
purify recep-tors from tissue extracts; consequently, receptors were discovered
after the drugs that bind to them. However, advances in molecular biology and
genome sequencing have effectively reversed this order. Now receptors are being
discovered by predicted structure or sequence homology to other (known)
receptors, and drugs that bind to them are developed later using chemical
screening meth-ods. This effort has revealed, for many known drugs, a larger
diversity of receptors than previously anticipated. It has also iden-tified a
number of “orphan” receptors,
so-called because their ligands are presently unknown, which may prove to be
useful targets for the development of new drugs.The best-characterized drug
receptors are regulatory proteins,
which mediate the actions of endogenous chemical signals such as
neurotransmitters, autacoids, and hormones. This class of recep-tors mediates
the effects of many of the most useful therapeutic agents. The molecular
structures and biochemical mechanisms of these regulatory receptors are described
in a later section entitled Signaling Mechanisms & Drug Action.
Other
classes of proteins that have been clearly identified as drug receptors include
enzymes, which may be inhibited (or,
less commonly, activated) by binding a drug (eg, dihydrofolate reductase, the
receptor for the antineoplastic drug methotrexate); transport proteins (eg, Na+/K+-ATPase, the membrane
receptorfor cardioactive digitalis glycosides); and structural proteins (eg, tubulin, the receptor for colchicine, an
anti-inflammatory agent).
This
sections deals with three aspects of drug receptor function, presented in
increasing order of complexity: (1) receptors as deter-minants of the
quantitative relation between the concentration of a drug and the pharmacologic
response, (2) receptors as regulatory proteins and components of chemical
signaling mechanisms that provide targets for important drugs, and (3)
receptors as key deter-minants of the therapeutic and toxic effects of drugs in
patients.
Related Topics
Privacy Policy, Terms and Conditions, DMCA Policy and Compliant
Copyright © 2018-2023 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.