Alpha-2 adrenergic receptor

The α₂ receptor is a type of adrenergic receptor.

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 (α_2A; ADRA2A) [Goodman Gilman, Alfred. "Goodman & Gilman's The Pharmacological Basis of Therapeutics". Tenth Edition. McGraw-Hill (2001): Page 140.]
* Vasoconstriction of arteries (α_2B; ADRA2B) to heart (coronary artery).cite journal | author = Woodman OL, Vatner SF | title = Coronary vasoconstriction mediated by α₁- and α₂-adrenoceptors in conscious dogs | journal = Am. J. Physiol. | volume = 253 | issue = 2 Pt 2 | pages = H388–93 | year = 1987 | pmid = 2887122 | doi = | issn = | url = http://ajpheart.physiology.org/cgi/content/abstract/253/2/H388 ]
* Vasoconstriction of veinscite journal | author = Elliott J | title = Alpha-adrenoceptors in equine digital veins: evidence for the presence of both α₁ and α₂-receptors mediating vasoconstriction | journal = J. Vet. Pharmacol. Ther. | volume = 20 | issue = 4 | pages = 308–17 | year = 1997 | pmid = 9280371 | doi = 10.1046/j.1365-2885.1997.00078.x | issn = ]
* Decrease motility of smooth muscle in gastrointestinal tractcite journal | author = Sagrada A, Fargeas MJ, Bueno L | title = Involvement of α₁ and α₂ adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat | journal = Gut | volume = 28 | issue = 8 | pages = 955–9 | year = 1987 | pmid = 2889649 | doi = 10.1136/gut.28.8.955 | issn = ]
* 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
**Decrease release of norepinephrine
***Inhibit norepinephrine system in brain
* Inhibitioncite journal | author = Wright EE, Simpson ER | title = Inhibition of the lipolytic action of beta-adrenergic agonists in human adipocytes by alpha-adrenergic agonists | journal = J. Lipid Res. | volume = 22 | issue = 8 | pages = 1265–70 | year = 1981 | pmid = 6119348 | doi = | issn = | url = http://www.jlr.org/cgi/content/abstract/22/8/1265] of lipolysis in adipose tissue.
* inhibition of insulin release in pancreas.cite book | author = Fitzpatrick, David; Purves, Dale; Augustine, George | title = Neuroscience | publisher = Sinauer | location = Sunderland, Mass | year = 2004 | | edition = Third Edition | chapter = Table 20:2 | pages = | isbn = 0-87893-725-0 | oclc = | doi = ]
* induction of glucagon release from pancreas.
* platelet aggregation
* contraction of sphincters of the gastrointestinal tract
* ↓ Secretion from salivary glandcite journal | author = Khan ZP, Ferguson CN, Jones RM | title = alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role | journal = Anaesthesia | volume = 54 | issue = 2 | pages = 146–65 | year = 1999 | pmid = 10215710 | doi = 10.1046/j.1365-2044.1999.00659.x | issn = ]
* relax gastrointestinal tract(presynaptic effect)

Mechanism

A G protein - G_i renders adenylate cyclase inactivated, resulting in decrease of cAMP.

The relaxation of gastrointestinal tract motility is by presynaptic inhibition cite book |author=Rang, H. P. |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages= |isbn=0-443-07145-4 |oclc= |doi= Page 163 ] , 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. Other agonists include:
* clonidine* (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)
* tizanidine (in spasms, cramping)
* guanfacine (antihypertensive)

* denotes selective agonists to the receptor.

***Clonidine is an Alpha 2 Agonist ; initially thought act via presynaptic 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

"(Alpha blockers)"
* yohimbine* (purported aphrodisiac)
* mirtazapine (NaSSA)
* mianserin (tetracyclic antidepressant)
* idazoxan*(experimental) [ [http://www.online-medical-dictionary.org/Idazoxan.asp?q=Idazoxan online-medical-dictionary.org] ]

* denotes selective agonists to the receptor.

Types

There are three types of α₂ receptors: ADRA2A, ADRA2B, ADRA2C.

ee also

*Other adrenergic receptors
**Alpha-1 adrenergic receptor
**Beta-1 adrenergic receptor
**Beta-2 adrenergic receptor
**Beta-3 adrenergic receptor

References