Alpha-1 adrenergic receptor

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The alpha-1 adrenergic receptor1-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:

Specific

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

Smooth muscle

In smooth muscle of blood vessels the principal effect is vasoconstriction. Blood vessels with α1 receptors are present in the skin, the sphincters[4] of gastrointestinal system, kidney (renal artery)[5] and brain.[6] 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 bladder[7][8], 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:

In a few areas the result on smooth muscle is relaxation. These include:

Other

  • 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, Gq, activates phospholipase C (PLC), which causes an increase in IP3 and calcium. This triggers all other effects.

Agonists

Agonists include:

* denotes selective agonists to the receptor.

Noradrenaline has higher receptor affinity than has adrenaline, which, in turn has much higher affinity than isoprenaline.[4]

Antagonsts

Antagonists are various alpha blockers:

* denotes selective agonists to the receptor.

Subtypes

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

See also

References

  1. 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.
  2. 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:10.1046/j.1365-2885.1997.00078.x. PMID 9280371.
  3. 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:10.1136/gut.28.8.955. PMID 2889649.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163
  5. Schmitz JM, Graham RM, Sagalowsky A, Pettinger WA (1981). "Renal α1 and α2 adrenergic receptors: biochemical and pharmacological correlations". J. Pharmacol. Exp. Ther. 219 (2): 400–6. PMID 6270306.
  6. Circulation & Lung Physiology I M.A.S.T.E.R. Learning Program, UC Davis School of Medicine
  7. 7.0 7.1 7.2 7.3 7.4 7.5 7.6 Fitzpatrick, David; Purves, Dale; Augustine, George (2004). "Table 20:2". Neuroscience (Third Edition ed.). Sunderland, Mass: Sinauer. ISBN 0-87893-725-0.
  8. Chou EC, Capello SA, Levin RM, Longhurst PA (2003). "Excitatory α1-adrenergic receptors predominate over inhibitory β-receptors in rabbit dorsal detrusor". J. Urol. 170 (6 Pt 1): 2503–7. doi:10.1097/01.ju.0000094184.97133.69. PMID 14634460.
  9. Morton JS, Daly CJ, Jackson VM, McGrath JC (2007). "Alpha1A-adrenoceptors mediate contractions to phenylephrine in rabbit penile arteries". Br. J. Pharmacol. 150 (1): 112–20. doi:10.1038/sj.bjp.0706956. PMID 17115072.
  10. 10.0 10.1 Walter F., PhD. Boron. Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 787

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