, a receptor
is a protein
molecule, embedded in either the plasma membrane
of a cell, to which a mobile signaling (or "signal") molecule may attach. A molecule which binds to a receptor is called a "ligand
," and may be a peptide (such as a neurotransmitter
), a hormone
, a pharmaceutical drug, or a toxin, and when such binding occurs, the receptor undergoes a conformational change which ordinarily initiates a cellular response. However, some ligands merely block receptors without inducing any response (e.g. antagonists). Ligand-induced changes in receptors result in physiological changes which constitute the biological activity of the ligands.
The shapes and actions of receptors are studied by X-ray crystallography
and computer modelling, which have advanced the understanding of drug action
at the binding sites of receptors.
Depending on their functions and ligands, several types of receptors may be identified:
Binding and activation
Ligand binding is an equilibrium
process. Ligands bind to receptors and dissociate from them according to the law of mass action
- (the brackets stand for concentrations)
One measure of how well a molecule fits a receptor is the binding affinity, which is inversely related to the dissociation constant Kd. A good fit corresponds with high affinity and low Kd. The final biological response (e.g. second messenger cascade or muscle contraction), is only achieved after a significant number of receptors are activated.
If the receptor exists in two states (see this picture), then the ligand binding must account for these two receptor states. For a more detailed discussion of two-state binding, which is thought to occur as an activation mechanism in many receptors see this link
A receptor which is capable of producing its biological response in the absence of a bound ligand is said to display "constitutive activity." The constitutive activity of receptors may be blocked by inverse agonist
binding. Mutations in receptors that result in increased constitutive activity underlie some inherited diseases, such as precocious puberty (due to mutations in luteinizing hormone receptors) and hyperthyroidism (due to mutations in thyroid-stimulating hormone receptors). Psychostimulants
act as inverse agonists on dopamine receptors
For the use of statistical mechanics in a quantitative study of the
ligand-receptor binding affinity, see the comprehensive article on the configuration integral.
Not every ligand that binds to a receptor also activates the receptor. The following classes of ligands exist:
- (Full) agonists are able to activate the receptor and result in a maximal biological response. Most natural ligands are full agonists.
- Partial agonists do not activate receptors thoroughly, causing responses which are partial compared to those of full agonists.
- Antagonists bind to receptors but do not activate them. This results in receptor blockage, inhibiting the binding of other agonists.
- Inverse agonists reduce the activity of receptors by inhibiting their constitutive activity.
Peripheral membrane protein receptors
G protein-coupled receptors
These receptors are also known as seven transmembrane receptors
receptors, because they pass through the membrane seven times.
Receptor tyrosine kinases
These receptors detect ligands and propagate signals via the tyrosine kinase
of their intracellular domains.
This family of receptors includes;
Guanylyl cyclase receptors
Ionotropic receptors are heteromeric
or homomeric oligomers
. They are receptors that respond to extracellular ligands and receptors that respond to intracellular ligands.
|| Ion current |
| Nicotinic acetylcholine receptor
|| Acetylcholine, Nicotine
|| Na+, K+, Ca2+ |
| Glycine receptor (GlyR)
|| Glycine, Strychnine
|| Cl- > HCO-3 |
| GABA receptors: GABA-A, GABA-C
|| Cl- > HCO-3 |
| Glutamate receptors: NMDA receptor, AMPA receptor, and Kainate receptor
|| Na+, K+, Ca2+ |
| 5-HT3 receptor
|| Na+, K+ |
| P2X receptors
|| Ca2+, Na+, Mg2+ |
The entire repertoire of human plasma membrane receptors is listed at the Human Plasma Membrane Receptome (http://www.receptome.org).
Role in Genetic Disorders
Many genetic disorders
involve hereditary defects in receptor genes. Often, it is hard to determine whether the receptor is nonfunctional or the hormone
is produced at decreased level; this gives rise to the "pseudo-hypo-" group of endocrine disorders
, where there appears to be a decreased hormonal level while in fact it is the receptor that is not responding sufficiently to the hormone.
Cells can increase (upregulate
) or decrease (downregulate
) the number of receptors to a given hormone
to alter its sensitivity to this molecule. This is a locally acting feedback
Ligand-bound desensitation of receptors was first characterized by Katz and Thesleff in the nicotine acetylcholine receptor
Prolonged or repeated exposure to a stimulus often results in decreased responsiveness of that receptor for a stimulus. Receptor desensitization results in altered affinity for the ligand. Receptor desensitization can modeled by a two-state model that also predicts that antagonists combined with agonists can prevent receptor desensitization See this link
for detailed molecular description
Desensitation may be accomplished by
- Receptor phosphorylation.
- Uncoupling of receptor effector molecules.
- Receptor sequestration (internalization).
In immune system
The main receptors in the immune system
are pattern recognition receptors
(PRRs), Toll-like receptors
(TLRs), killer activated
and killer inhibitor receptors
(KARs and KIRs), complement receptors
, Fc receptors
, B cell receptors
and T cell receptors