In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. Ligand-induced changes in the behavior of receptor proteins result in physiological changes that constitute the biological actions of the ligands.
A measure of how well a certain molecule fits into a given receptor is the binding affinity which is measured as the dissociation constant Kd (good fit means high affinity and a low Kd). The activation of the second messenger cascade and the final biological response is achieved only when at a certain time point a significant number of receptors are activated by bound ligands.
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 .
Receptors which are active in the absence of a ligand. The constitutive activity of these receptors may be reversed by inverse agonist binding. Mutations in receptors that result in increased constitutive receptor signaling underlie some heritable diseases, such as precocious puberty (luteinizing hormone receptor mutations) and hyperthyroidism (thyroid-stimulating hormone receptor mutations). Psychostimulants act as inverse agonists at dopamine receptors.
Not every ligand that binds to a receptor also activates the receptor. The following classes of ligands exist:
The shapes and actions of receptors are newly investigated by the X-ray crystallography and computer modelling. This increases the current understanding of drug action at binding sites on the receptors.
Receptors exist in different types, dependent on their ligand and function:
These receptors are also known as seven transmembrane receptors or 7TM receptors.
These receptors detect ligands and propagate signals via the tyrosine kinase of their intracellular domains. This family of receptors includes;
|Nicotinic acetylcholine receptor||Acetylcholine, Nicotine||Na+, K+, Ca2+ |
|Glycine receptor (GlyR)||Glycine, Strychnine||Cl- > HCO-3 |
|GABA receptors: GABA-A, GABA-C||GABA||Cl- > HCO-3 |
|Glutamate receptors: NMDA receptor, AMPA receptor, and Kainate receptor||Glutamate||Na+, K+, Ca2+ |
|5-HT3 receptor||Serotonin||Na+, K+ |
|P2X receptors||ATP||Ca2+, Na+, Mg2+ |
|cyclic nucleotide-gated ion channels||cGMP (vision), cAMP and cGTP (olfaction)||Na+, K+ |
|IP3 receptor||IP3||Ca2+ |
|Intracellular ATP receptors||ATP (closes channel)||K+ |
|Ryanodine receptor||Ca2+||Ca2+ |
The entire repertoire of human plasma membrane receptors is listed at the Human Plasma Membrane Receptome (http://receptome.stanford.edu).
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 or neurotransmitter to alter its sensitivity to this molecule. This is a locally acting feedback mechanism.
Ligand-bound desensitation of receptors was first characterized by Katz and Thesleff in the nicotine acetylcholine receptor Prolonged or repeat 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
The content of this section is licensed under the GNU Free Documentation License (local copy). It uses material from the Wikipedia article "Receptor (biochemistry)" modified December 22, 2007 with previous authors listed in its history.