Receptor (biochemistry)

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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.

1 Overview
2 Peripheral membrane protein receptors
3 Transmembrane receptors
- 3.1 Metabotropic receptors
- 3.2 Ionotropic receptors
4 Intracellular receptors
- 4.1 Transcription factors
- 4.2 Various
5 Role in Genetic Disorders
6 Receptor Regulation
7 See also
8 External links

[edit] Overview

Transmembrane receptor:E=extracellular space; I=intracellular space; P=plasma membrane

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 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 hormone receptors. These receptors often can enter the cell nucleus and modulate gene expression in response to the activation by the ligand.
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.

[edit] Peripheral membrane protein receptors

[edit] Transmembrane receptors

[edit] Metabotropic receptors

[edit] G-protein-coupled receptors

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

"muscarinic" Acetylcholine receptors (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 ...

[edit] 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
IGF-1 Receptor
various other receptors for growth factors & cytokines
...

[edit] Guanylyl cyclase receptors

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

[edit] Ionotropic receptors

Nicotinic acetylcholine receptors (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).

[edit] Intracellular receptors

[edit] Transcription factors

Steroid hormone receptor:
Thyroid hormone receptor
Retinoid receptor (vitamin A and related compounds);
Peroxisome proliferator-activated receptors (PPARs)

[edit] Various

sigma</sub>1</sub> (neurosteroids))
IP₃ receptor (inositol triphosphate, IP₃)

[edit] 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.

[edit] 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.

[edit] Mechanism

For insulin, the process of down regulation occurs when there are elevated levels of the hormone in the blood. When insulin binds to its receptors on the surface of a cell endocytosis of the hormone receptor complex is initiated, only to be subsequently attacked by intracellular lysosomal enzymes. The internalization is multi-purposed as it provides the pathway for degradation of the hormone, and also a way to regulate the number of sites that are available for binding on the cell’s surface. At high plasma concentrations, the number of surface receptors for insulin is gradually reduced by the accelerated rate of receptor internalization and degradation brought about by increased hormonal binding. The rate of synthesis of new receptors within the endoplasmic reticulum and their insertion in the plasma membrane do not keep pace with their rate of destruction. Over time, this self-induced loss of target cell receptors for insulin reduces the target cell’s sensitivity to the elevated hormone concentration. The process of decreasing the number of receptor sites is virtually the same for all hormones it only varies in the receptor hormone complex.

[edit] Cases

To illustrate this process we shall look at the insulin receptor sites on the target cells of a Type II diabetic. Due to the elevated levels of blood glucose from excessive feeding in an overweight individual the β-cells (islets of Langerhans) in the pancreas must release more insulin than normally emitted to match the demand and return the blood to homeostatic levels. The near constant increase in blood insulin levels results from an effort to match the increase in blood glucose which will cause receptor sites on the person’s cell to down-regulate and decrease the number of receptors for insulin, increasing the subject’s resistance by decreasing sensitivity to this hormone. There is also a hepatic decrease in sensitivity to insulin. This can be seen in the continuing gluconeogenesis in the liver even when blood glucose levels are elevated. This is the more common process of insulin resistance, which in turn leads to a case of adult onset diabetes in that subject. Other cases include Diabetes insipidus; here the kidneys become insensitive to arginine vasopressin.

[edit] Reversal

There are ways to counteract this process; using the previous example a Type II diabetic may increase their sensitivity to insulin through proper diet and regular exercise producing weight loss, some may even return to their pre-diabetic state following this regimen.

[edit] Reference

Sherwood, L. (2004). “Human Physiology From Cells to Systems, 5th Ed” (p. 680). Belmont, CA: Brooks/Cole-Thomson Learning

Wilmore, J., Costill, D. (2004). Physiology of Sport and Exercise, 3rd Ed (p. 164). Champaign, IL: Human Kinetics

[edit] See also

[edit] External links

Cell signaling
Key concepts - Ligand \| Receptor \| Second messenger \| Protein kinase \| Transcription factor \| Cell signaling networks
Pathways - Apoptosis \| Ca²⁺ signaling \| Cytokine signaling \| Hedgehog \| Integrin signaling \| JAK/STAT \| Lipid signaling \| MAPK/ERK pathway \| mTOR \| NF-kB \| Notch \| p53 \| TGFβ \| Wnt