Alpha-1 adrenergic receptor

Sabah Mansoor

2014-PhD-1070

Alpha-1 adrenergic receptor

• alpha-1 (α1) adrenergic receptor is a G protein Coupled

Receptor (GPCR) associated with the Gq, heterotrimeric

protein.

• more responsive to Norepinephrine than to epinephrine.

• Catecholamines like norepinephrine (noradrenaline) and

epinephrine (adrenaline) signal through the α1-adrenergic

receptor in the central and peripheral nervous systems.

Types of alpha receptors

• α-adrenoceptors exist on peripheral sympathetic nerve

terminals and are divided into two subtypes α1, and α2.

• α1 is found mostly postsynaptically, whilst α2 although

typically sited presynaptically, can also occur

postsynaptically.

• Alpha 1 adrenergic receptor consists of three highly

homologous subtypes, including α1A, α1B, α1D- adrenergic.

α-Adrenoceptor Location and function

Alpha 1 receptors are located on:

• all vascular smooth muscle, although densities vary

throughout the body

• GI & urinary sphincters

• dilator muscle of the iris

• arrector pili muscle of hair follicles

• On central and peripheral nervous system

• In the Central Nervous System they are found mostly

postsynaptically and have an excitatory function.

• Peripherally they are responsible for contraction and are

situated on vascular and on non-vascular smooth muscle.

• α1-adrenoceptors on vascular smooth muscle are located

intrasynaptically and function in response to neurotransmitter

release.

• For non-vascular smooth muscle they can be found on the

liver, where they cause hepatic glycogenolysis and potassium

release. On the heart they mediate a positive inotropic effect.

• Cause relaxation of Gastro Intestinal smooth muscle and

decrease salivary secretion.

Signaling Cascade

agonists and antigonists

Alpha 1 agonists

vasoconstrictive agents they are used to reduce edema and

inflammation. naphazoline, phenylephrine and

propylhexedrine.

Alpha 1 antagonists

causes vasodilation and decreased peripheral resistance;

therefore they are used in the treatment of hypertension

(prazosin). Treatment of benign prostatic hyperplasia.

tamsulosin is a subtype-selective alpha 1A receptor that has

more specificity toward smooth muscle in genitourinary

tract.

REFERENCES

• Stedeford T, Cardozo-PF, Vultaggio B, Muro CC, Luzardo GE, Harbison

RD. 2001. Alpha1-andrenergic receptors and their significance to

chemical-induced nephrotoxicity—a brief review. Res. Commun. Mol.

Pathol. Pharmacol. 110 (1-2): 59-72.

• Chen ZJ, Minneman KP. 2005. Recent progress in alpha 1-andrenergic

receptor research. Acta Pharmacol Sin. 26 (11): 1281-7.

• Piascik MT, Perez DM. 2001. Alpha1-angrenergic receptors: new

insights and directions. J. Pharmacol. Exp. Ther. 298 (2): 403-10.

• Sushmita P,Peter BR. 2011. The functional role of the alpha-1

andrenergic receptors in cerebral blood flow regulation. Indian J.

Pharmacol. 43 (5): 502-506.