Alpha-1 adrenergic receptor

The alpha-1 adrenergic receptor (α₁-AR) is an adrenergic receptor with the primary effect of vasoconstriction.

Effect

The α₁ receptor has several, general, functions in common with other α-receptors, but also has specific effects.

General

Common (or still unspecified) effects include:
* Vasoconstriction of arteries to heart (coronary arteries).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 ]
* Venoconstriction 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 = ]

pecific

The primary effect is on smooth muscle, which mainly constrict. However, there are other functions as well.

mooth muscle

In smooth muscle of blood vessels the principal effect is vasoconstriction. Blood vessels with α₁ receptors are present in the skin, the sphincters of gastrointestinal system, kidney (renal artery)cite journal | author = Schmitz JM, Graham RM, Sagalowsky A, Pettinger WA | title = Renal α₁ and α₂ adrenergic receptors: biochemical and pharmacological correlations | journal = J. Pharmacol. Exp. Ther. | volume = 219 | issue = 2 | pages = 400–6 | year = 1981 | pmid = 6270306 | doi = | issn = | url = http://jpet.aspetjournals.org/cgi/content/abstract/219/2/400 ] and brain. [ [http://cim.ucdavis.edu/masters/sessions2002/session4_ica.doc Circulation & Lung Physiology I] M.A.S.T.E.R. Learning Program, UC Davis School of Medicine] During the fight-or-flight response vasoconstriction results in the decreased blood flow to these organs. This accounts for an individual's skin appearing pale when frightened.

It also induces contraction of the urinary bladdercite 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 = ] cite journal | author = Chou EC, Capello SA, Levin RM, Longhurst PA | title = Excitatory α₁-adrenergic receptors predominate over inhibitory β-receptors in rabbit dorsal detrusor | journal = J. Urol. | volume = 170 | issue = 6 Pt 1 | pages = 2503–7 | year = 2003 | pmid = 14634460 | doi = 10.1097/01.ju.0000094184.97133.69 | issn = ] , although this effect is minor compared to the relaxing effect of β-2 adrenergic receptors. In other words, the overall effect of sympathetic stimuli on the bladder is relaxation, in order to delay micturition during stress.

Other effects are on smooth muscle are contraction in:
*ureter
*hairs (arrector pili muscles)
*uterus (when pregnant)
*urethral sphincter
*bronchioles (although minor to the relaxing effect of β₂ receptor on bronchioles)
*iris dilator muscle 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 ]
*seminal tract, resulting in ejaculation

In a few areas the result on smooth muscle is relaxation. These include:
*The rest of the GI tract than the sphincters.
*Blood vessels of erectile tissue.cite journal | author = Morton JS, Daly CJ, Jackson VM, McGrath JC | title = Alpha_1A-adrenoceptors mediate contractions to phenylephrine in rabbit penile arteries | journal = Br. J. Pharmacol. | volume = 150 | issue = 1 | pages = 112–20 | year = 2007 | pmid = 17115072 | doi = 10.1038/sj.bjp.0706956 | issn = ]

Other

*Positive ionotropic effect on heart muscle. (α₁<<β₁).

*&uarr;Secretion from salivary gland.

*Increase salivary potassium levels.

*Glycogenolysis and gluconeogenesis from adipose tissue and liver.

*Secretion from sweat glands.

*Na⁺ reabsorption from kidney.
**Stimulate proximal tubule NHE3 cite book |author=Walter F., PhD. Boron |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |location= |year= |pages= |isbn=1-4160-2328-3 |oclc= |doi= Page 787 ]
**Stimulate proximal tubule basolateral Na-K ATPase

*Activate mitogenic responses and regulate growth and proliferation of many cells.

Activity During Exercise

During exercise these alpha-1 receptors can be selectively blocked by sympathetic nervous activity, allowing the beta-2 receptors (which mediate vasodilation) to dominate. Note that only the alpha-1 receptors in exercising muscle will be blocked. Resting muscle will not have its alpha-1 receptors blocked, and hence the overall effect there will be alpha-1 mediated vasocontriction.

Mechanism

Alpha₁-adrenergic receptors are members of the G protein-coupled receptor superfamily. Upon activation, a heterotrimeric G protein, G_q, activates phospholipase C (PLC), which causes an increase in IP₃ and calcium. This triggers all other effects.

Agonists

Agonists include:
* noradrenaline
* adrenaline
* isoprenaline
* phenylephrine* (decongestant)
* methoxamine*
* cirazoline*

* denotes selective agonists to the receptor.

Noradrenaline has higher receptor affinity than has adrenaline, which, in turn has much higher affinity than isoprenaline.

Antagonists

Antagonists are various "alpha blockers:
*mirtazapine (NaSSA)
*phenoxybenzamine (in hypertension)
*phentolamine (in hypertensive emergencies)
*prazosin* (in hypertension)
*tamsulosin (in BPH)
*terazosin (in BPH and hypertension)
*doxazocin* (in BPH and hypertension)

* denotes selective antagonists to the receptor.

ubtypes

There are 3 α₁-AR subtypes: alpha-1A, -1B and -1D, all of which signal through the G_q/11 family of G-proteins and different subtypes show different patterns of activation.

ee also

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

References