receptor: Definition and Much More from Answers.com

Wikipedia: receptor (biochemistry)

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.

Binding and activation

Ligand binding to a receptor is an equilibrium process: Ligands bind to an empty receptor and they dissociate from it (according to the law of mass action):

Failed to parse (unknown function\overset): \left [ Ligand \right ] \cdot \left [ Receptor \right ] \overset{ K_d}{ \rightleftharpoons } \left [ Ligand-receptor complex \right ]

(the brackets stand for concentrations)

A measure of how well a certain molecule fits into a given receptor is the binding affinity which is measured as the dissociation constant K_d (good fit means high affinity and a low K_d). 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.

Agonists versus antagonists

Not every ligand that binds to a receptor it 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 are not able to activate the receptor maximally, resulting in a partial biological response compared to a full agonist.
• Antagonists bind to the receptor but do not activate it. This results in a receptor blockade that inhibits the binding of agonists.
• Inverse agonists are antagonists that are able to further reduce the receptor activation by decreasing its basal activity

Overview

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:

• Some receptor proteins are peripheral membrane proteins;
• Many hormone receptors and neurotransmitter receptors are transmembrane proteins: transmembrane receptors are embedded in the lipid bilayer of cell membranes, that allow the activation of signal transduction pathways in response to the activation by the binding molecule, or ligand.
  • Metabotropic receptors are coupled to G proteins and affect the cell indirectly through enzymes which control ion channels.
  • Ionotropic receptors contain a central pore which functions as a ligand-gated ion channel.
• Another major class of receptors are intracellular proteins such as those for steroid and intracrine peptide hormone receptors. These receptors often can enter the cell nucleus and modulate gene expression in response to the activation by the ligand.

Peripheral membrane protein receptors

See also: Peripheral membrane protein

Transmembrane receptors

Metabotropic receptors

G protein-coupled receptors

These receptors are also known as seven transmembrane receptors or 7TM receptors.

• Muscarinic acetylcholine receptor (Acetylcholine and Muscarine)
• Adenosine receptors (Adenosine)
• Adrenoceptors (also known as Adrenergic receptors, for adrenaline, and other structurally related hormones and drugs)
• GABA receptors, Type-B (γ-Aminobutyric acid or GABA)
• Angiotensin receptors (Angiotensin)
• Cannabinoid receptors (Cannabinoids)
• Cholecystokinin receptors (Cholecystokinin)
• Dopamine receptors (Dopamine)
• Glucagon receptors (Glucagon)
• Metabotropic glutamate receptors (Glutamate)
• Histamine receptors (Histamine)
• Olfactory receptors (for the sense of smell)
• Opioid receptors (Opioids)
• Rhodopsin (a photoreceptor)
• Secretin receptors (Secretin)
• Serotonin receptors, except Type-3 (Serotonin, also known as 5-Hydroxytryptamine or 5-HT)
• Somatostatin receptors (Somatostatin)
• Calcium-sensing receptor (Calcium)
• Chemokine receptors (Chemokines)
• many more ...

Receptor tyrosine kinases

These receptors detect ligands and propagate signals via the tyrosine kinase of their intracellular domains. This family of receptors includes;

• Erythropoietin receptor (Erythropoietin)
• Insulin receptor (Insulin)
• Eph receptors
• Insulin-like growth factor 1 receptor
• various other receptors for growth factors & cytokines
• ....

Guanylyl cyclase receptors

• GC-A & GC-B: receptors for Atrial-natriuretic peptide (ANP) and other natriuretic peptides
• GC-C: Guanylin receptor

Ionotropic receptors

• Nicotinic acetylcholine receptor (Acetylcholine, Nicotine)
• Glycine receptor (GlyR) (Glycine, Strychnine)
• GABA receptors: GABA-A, GABA-C (GABA)
• Glutamate receptors: NMDA receptor, AMPA receptor, and Kainate receptor (Glutamate)
• 5-HT₃ receptor (Serotonin)

The entire repertoire of human plasma membrane receptors is listed at the Human Plasma Membrane Receptome (http://receptome.stanford.edu).

Intracellular receptors

Transcription factors

• nuclear receptor:
  • Steroid hormone receptor

Various

• sigma1 (neurosteroids))
• IP₃ receptor (inositol triphosphate, IP₃)
• G protein-coupled receptors PMID 16902576

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.

Receptor Regulation

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.

Receptor desensitization

Ligand-bound desensitation of receptors was first characterized by Katz and Thesleff in the nicotine acetylcholine receptor^[1][2] 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.^[1]

May be accomplished by

• Receptor phosphorylation.^[3]
• Uncoupling of receptor effector molecules.
• Receptor sequestration (internalization).^[3]

See also

• Signal transduction
• Neuropsychopharmacology
• Schild regression for ligand receptor inhibition
• K_i Database

References

1. ^ ^{a b} Y. Sun, R. Olson, M. Horning, N. Armstrong, M. Mayer and E. Gouaux. (2002) Mechanism of glutamate receptor desensitization Nature 417, 245-253
2. ^ S. Pitchford, J.W. Day, A. Gordon and D. Mochly-Rosen. (1992) Acetylcholine receptor desensitization is Regulate by activation-induced extracellular adenosine accumulation. The Journal of Neuroscience, 1.311): 4540-4544.
3. ^ ^{a b} G. Boulay, L. Chrbtien, D.E. Richard, AND G. Guillemettes. (1994) Short-Term Desensitization of the Angiotensin II Receptor of Bovine Adrenal Glomerulosa Cells Corresponds to a Shift from a High to a Low Affinity State. Endocrinology Vol. 135. No. 5 2130-2136

External links

• IUPHAR GPCR Database and Ion Channels Compendium
• MeSH Cell+surface+receptors

Cell physiology: cell signaling
Key concepts	Ligand - Cell signaling networks - Signal transduction - Apoptosis - Second messenger system (Ca2+ signaling, Lipid signaling)
Processes	Paracrine - Autocrine - Juxtacrine - Neurotransmitters - Endocrine (Neuroendocrine)
Types of proteins	Receptor (Transmembrane, Intracellular) - Transcription factor (General, Preinitiation complex, TFIID, TFIIH) - Adaptor protein

Translations: Translations for: Receptor