The α2 receptor is a type of adrenergic receptor.
Contents |
Effect
The α2 receptor has several, general, functions in common with other α-receptors, but also has individual effects.
General
Common (or still unspecified) effects include:
- Vasodilation of arteries (α2A; ADRA2A)[1]
- Vasoconstriction of arteries (α2B; ADRA2B) to heart (coronary artery).[2]
- Vasoconstriction of veins[3]
- Decrease motility of smooth muscle in gastrointestinal tract[4]
- Contraction of male genitalia during ejaculation
Individual
Individual actions of the α2 receptor include:
- Mediates synaptic transmission in pre- and postsynaptic nerve terminals.
- Decrease release of acetylcholine[5]
- Decrease release of norepinephrine[5]
- Inhibit norepinephrine system in brain
- Inhibition[6] of lipolysis in adipose tissue.[7]
- inhibition of insulin release in pancreas.[7]
- induction of glucagon release from pancreas.
- platelet aggregation
- contraction of sphincters of the gastrointestinal tract
- ↓ secretion from salivary gland[8]
- relax gastrointestinal tract(presynaptic effect)
Mechanism
The alpha subunit of an inhibitory G protein - Gi dissociated from the G protein, and associates with adenyl cyclase (also known as adenylate cyclase or adenylyl cyclase). This causes the inactivation of adenyl cyclase, resulting in a decrease of cAMP produced from ATP. This leads to a decrease of intracellular cAMP. Protein Kinase A is not able to be activated by cAMP, and so phosphorylase kinase cannot be phosphorylated by PKA. Phosphorylase kinase is responsible for the phosphorylation of proteins, and so there is a decrease in the levels of phosphorylated proteins, and the eventual cell response is decreased.
The relaxation of gastrointestinal tract motility is by presynaptic inhibition[5], where transmitters inhibit further release by homotropic effects.
Agonists
Epinephrine has higher affinity for the alpha-2 receptor than has norepinephrine, which, in turn, has much higher affinity than has isoprenaline.[5] Other agonists include:
- Nonselective
- clonidine*[5] (antihypertensive) -- see below for alternative mechanism --
- dexmedetomidine
- lofexidine (antihypertensive)
- xylazine (veterinary; in non-human species this is an immobilizing and anesthetic drug, presumptively also mediated by alpha-2 adrenergic receptors because it is reversed by yohimbine)
- TDIQ (partial agonist)
- tizanidine (in spasms, cramping)
- UK-14,304
- α2A selective
- guanfacine (antihypertensive)
- octopamine (also β3 agonist)
- α2C selective
* denotes selective agonists to the receptor.
-
-
- Clonidine is an Alpha 2 Agonist ; initially thought act via postsynaptic Alpha 2 receptors → reduced NE discharge. However! It binds to imidazoline receptors with a much greater affinity than Alpha 2s . Imidazoline Receptors occur in the Nucleus Tractus Solitarius & Ventrolateral Medulla. Clonidine is now thought to decrease BP via this central mechanism. ***
-
Antagonists
- Nonselective
- A-80426
- atipamezole
- efaroxan
- idazoxan*[5](experimental)[9]
- mirtazapine (tetracyclic antidepressant)
- mianserin (tetracyclic antidepressant)
- SB-269,970
- yohimbine*[5] (purported aphrodisiac)
- α2A selective
- BRL-44408
- RX-821,002
- α2B selective
- ARC-239
- imiloxan
- α2C selective
- JP-1302
- spiroxatrine (also serotonin 5-HT1A antagonist)
* denotes selective agonists to the receptor.
Types
There are three types of α2 receptors in humans; ADRA2A, ADRA2B and ADRA2C. Some other species express a fourth α2D subtype also.[10]
See also
- Other adrenergic receptors
References
- ^ Goodman Gilman, Alfred. Goodman & Gilman's The Pharmacological Basis of Therapeutics. Tenth Edition. McGraw-Hill (2001): Page 140.
- ^ Woodman OL, Vatner SF (1987). "Coronary vasoconstriction mediated by α1- and α2-adrenoceptors in conscious dogs". Am. J. Physiol. 253 (2 Pt 2): H388–93. PMID 2887122. http://ajpheart.physiology.org/cgi/content/abstract/253/2/H388.
- ^ Elliott J (1997). "Alpha-adrenoceptors in equine digital veins: evidence for the presence of both α1 and α2-receptors mediating vasoconstriction". J. Vet. Pharmacol. Ther. 20 (4): 308–17. doi:. PMID 9280371.
- ^ Sagrada A, Fargeas MJ, Bueno L (1987). "Involvement of α1 and α2 adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat". Gut 28 (8): 955–9. doi:. PMID 2889649.
- ^ a b c d e f g Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163
- ^ Wright EE, Simpson ER (1981). "Inhibition of the lipolytic action of beta-adrenergic agonists in human adipocytes by alpha-adrenergic agonists". J. Lipid Res. 22 (8): 1265–70. PMID 6119348. http://www.jlr.org/cgi/content/abstract/22/8/1265.
- ^ a b Fitzpatrick, David; Purves, Dale; Augustine, George (2004). "Table 20:2". Neuroscience (Third ed.). Sunderland, Mass: Sinauer. ISBN 0-87893-725-0.
- ^ Khan ZP, Ferguson CN, Jones RM (1999). "alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role". Anaesthesia 54 (2): 146–65. doi:. PMID 10215710.
- ^ online-medical-dictionary.org
- ^ Ruuskanen JO, Xhaard H, Marjamäki A, Salaneck E, Salminen T, Yan YL, Postlethwait JH, Johnson MS, Larhammar D, Scheinin M (January 2004). "Identification of duplicated fourth alpha2-adrenergic receptor subtype by cloning and mapping of five receptor genes in zebrafish". Molecular Biology and Evolution 21 (1): 14–28. doi:. PMID 12949138.
External links
- "Adrenoceptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1274.
 |
This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it. |
This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)
