Fundamentals of Medicinal Chemistry

A.4 Receptors

Receptors are specific areas of certain proteins and glycoproteins that are found

either spanning cellular membranes or in the nuclei of living cells. Any endogen-

ous or exogenous chemical agent that binds to a receptor is known as aligand.

The general region on a receptor where a ligand binds is known as thebinding

domain. It should be noted that the termdomainis used to indicate any area of a

bio-macromolecule that is linked to a specific function of that molecule. The

binding of a drug to a receptor either inhibits or stimulates its action, which

ultimately results in the physiological responses that are characteristic of the

action of the drug. For example, some ligand–receptor interaction causes the

opening or closing of ion channels, whist some interactions result in the release

of so calledsecondary messengers, which promote a sequence of biochemical

events that result in an appropriate physiological response (Figure A4.1). The

mechanism by which the message carried by the ligand is translated through the

receptor into a physiological response is known assignal transduction.

Receptors are classified according to function into four so calledsuperfamilies

of receptors (Table A4.1). The members of a superfamily will all have the same

general structure and general mechanism of action. However, individual

members of a superfamily tend to exhibit variations in the amino acid residue

sequence in certain regions and also the sizes of their extracellular and intracel-

lular domains. Each of these superfamilies is sub-divided into a number of types

of receptor, whose members are usually defined by their endogenous ligand. For

example, all receptors that bind acetylcholine (ACh) are of the cholinergic type

and those that bind adrenaline and noradrenaline are of the adrenergic type.

These sub-types are further classified either according to the type of genetic code

responsible for their structure or after the exogenous ligands that selectively bind

to the receptor. For example, the endogenous ligand acetylcholine will bind to all

cholinergic receptors but the exogenic ligand nicotine will only bind to nicotinic

Ligand A

EXTRACELLULAR

FLUID

Secondary

messenger

Cascade of

biochemical

events

Physiological

response

INTRACELLULAR FLUID

Receptor

Figure A4.1 A schematic representation of signal transduction

246 APPENDIX 4 RECEPTORS