Adrenergic receptor

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The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline).

Many cells possess these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system. The sympathetic nervous system is responsible for the fight-or-flight response, which includes widening the pupils of the eye, mobilizing energy, and diverting blood flow from non-essential organs to skeletal muscle.


Raymond Ahlquist, Professor of Pharmacology at Medical College of Georgia, published a paper concerning adrenergic nervous transmission in 1948[1] but its significance was largely ignored at that time. However, in 1954 he was able to incorporate his findings in a textbook, Drill's Pharmacology in Medicine, and thereby firmly establish the essential role played by α and β receptor sites in the adrenaline/nor-adrenaline cellular mechanism. His discovery would revolutionise advances in pharmacotherapeutic research, allowing the selective design of specific molecules to target medical ailments rather than rely upon traditional research into the efficacy of pre-existing herbal medicines.


There are two main groups of adrenergic receptors, α and β, with several subtypes.

  • α receptors have the subtypes α1 (a Gq coupled receptor) and α2 (a Gi coupled receptor[2]). Phenylephrine is a selective agonist of the α receptor.
  • β receptors have the subtypes β1, β2 and β3. All three are linked to Gs proteins (although β2 also couples to Gi),[3] which in turn are linked to adenylate cyclase. Agonist binding thus causes a rise in the intracellular concentration of the second messenger cAMP. Downstream effectors of cAMP include cAMP-dependent protein kinase (PKA), which mediates some of the intracellular events following hormone binding. Isoprenaline is a non-selective agonist.
The mechanism of adrenergic receptors. Adrenaline or noradrenaline are receptor ligands to either α1, α2 or β-adrenergic receptors. α1 couples to Gq, which results in increased intracellular Ca2+ and subsequent smooth muscle contraction. α2, on the other hand, couples to Gi, which causes a decrease in neurotransmitter release, as well as a decrease of cAMP activity and a resulting and smooth muscle contraction. β receptors couple to Gs, and increases intracellular cAMP activity, resulting in e.g. heart muscle contraction, smooth muscle relaxation and glycogenolysis.

Roles in circulation[edit]

Epinephrine (adrenaline) reacts with both α- and β-adrenoreceptors, causing vasoconstriction and vasodilation, respectively. Although α receptors are less sensitive to epinephrine, when activated, they override the vasodilation mediated by β-adrenoreceptors because there are more peripheral α1 receptors than β-adrenoreceptors. The result is that high levels of circulating epinephrine cause vasoconstriction. At lower levels of circulating epinephrine, β-adrenoreceptor stimulation dominates, producing vasodilation followed by decrease of peripheral vascular resistance.


Smooth muscle behavior is variable depending on anatomical location. Smooth muscle contraction/relaxation is generalized below. One important note is the differential effects of increased cAMP in smooth muscle compared to cardiac muscle. Increased cAMP will promote relaxation in smooth muscle, while promoting increased contractility and pulse rate in cardiac muscle.

Receptor Agonist potency order Selected action
of agonist
Mechanism Agonists Antagonists
A, B, D
Norepinephrine > epinephrine >> isoprenaline Smooth muscle contraction, mydriasis, vasoconstriction in the skin, muscosa and abdominal viscera & sphincter contraction of the GI tract and urinary bladder Gq: phospholipase C (PLC) activated, IP3,and DAG, rise in calcium

(Alpha-1 agonists)

(Alpha-1 blockers)


Antihistamines (H1 antagonists)

A, B, C
Epinephrinenorepinephrine >> isoprenaline Smooth muscle mixed effects, norepinephrine (noradrenaline) inhibition, platelet activation Gi: adenylate cyclase inactivated, cAMP down

(Alpha-2 agonists)

(Alpha-2 blockers)
β1 Isoprenaline > epinephrine = norepinephrine Positive Chronotropic, Dromotropic and inotropic effects, increased amylase secretion Gs: adenylate cyclase activated, cAMP up (Beta blockers)
β2 Isoprenaline > epinephrine >> norepinephrine Smooth muscle relaxation (Ex. Bronchodilation) Gs: adenylate cyclase activated, cAMP up (also Gi, see α2) (Short/long) (Beta blockers)
β3 Isoprenaline = norepinephrine > epinephrine Enhance lipolysis, promotes relaxation of detrusor muscle in the bladder Gs: adenylate cyclase activated, cAMP up


There is no α1C receptor. At one time, there was a subtype known as C, but was found to be identical to one of the previously discovered subtypes. To avoid confusion, naming was continued with the letter D.

α receptors[edit]

α receptors have several functions in common, but also individual effects. Common (or still unspecified) effects include:

α1 receptor[edit]

α1-adrenergic receptors are members of the Gq protein-coupled receptor superfamily. Upon activation, a heterotrimeric G protein, Gq, activates phospholipase C (PLC). The PLC cleaves phosphatidylinositol 4,5-bisphosphate (PIP2), which in turn causes an increase in inositol triphosphate (IP3) and diacylglycerol (DAG). The former interacts with calcium channels of endoplasmic and sarcoplasmic reticulum, thus changing the calcium content in a cell. This triggers all other effects.

Specific actions of the α1 receptor mainly involve smooth muscle contraction. It causes vasoconstriction in many blood vessels, including those of the skin, gastrointestinal system, kidney (renal artery)[8] and brain.[9] Other areas of smooth muscle contraction are:

Further effects include glycogenolysis and gluconeogenesis from adipose tissue[11] and liver, as well as secretion from sweat glands[11] and Na+ reabsorption from kidney.[11]

Antagonists may be used primarily in hypertension, anxiety disorder, and panic attacks.

α2 receptor[edit]

The α2 receptor couples to the Gi/o protein.[2] It is a presynaptic receptor, causing negative feedback on, for example, norepinephrine. When NA is released into the synapse, it feeds back on the α2 receptor, causing less NA release from the presynaptic neuron. This decreases the effect of NA. There are also α2 receptors on the nerve terminal membrane of the post-synaptic adrenergic neuron.

There are 3 highly homologous subtypes of α2 receptors: α2A, α, and α2C.

Specific actions of the α2 receptor include:

  • inhibition of insulin release in the pancreas.[11]
  • induction of glucagon release from the pancreas.
  • contraction of sphincters of the gastrointestinal tract
  • negative feedback in the neuronal synapses - presynaptic inhibition of noradrenalin (NA) release in CNS
  • increased thrombocyte aggregation

β receptors[edit]

β1 receptor[edit]

Specific actions of the β1 receptor include:

  • Increase cardiac output by increasing heart rate (positive chronotropic effect), conduction velocity (positive dromotropic effect), and stroke volume (by enhancing contractility—positive inotropic effect).
  • Increase renin secretion from juxtaglomerular cells of the kidney.
  • Increase ghrelin secretion from the stomach.[12]

β2 receptor[edit]

Beta-2 adrenergic receptor (PDB 2rh1), which stimulates cells to increase energy production and utilization. The membrane is shown schematically with a gray stripe.

Specific actions of the β2 receptor include the following:

β3 receptor[edit]

Specific actions of the β3 receptor include:

  • Enhancement of lipolysis in adipose tissue. β3 activating drugs could theoretically be used as weight-loss agents, but are limited by the side effect of tremors.

See also[edit]


  1. ^ Ahlquist R.P. A Study of the Adenotrophic Receptors, Am. J. Physiol. 1948 153:586-600
  2. ^ a b Kou Qin, Pooja R. Sethi and Nevin A. Lambert (August 2008). "Abundance and stability of complexes containing inactive G protein-coupled receptors and G proteins". The FASEB Journal 22 (8): 2920–2927. doi:10.1096/fj.08-105775. PMID 18434433. 
  3. ^ Chen-Izu Y, Xiao RP, Izu LT, Cheng H, Kuschel M, Spurgeon H, Lakatta EG (November 2000). "G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels". Biophys. J. 79 (5): 2547–56. Bibcode:2000BpJ....79.2547C. doi:10.1016/S0006-3495(00)76495-2. PMC 1301137. PMID 11053129. 
  4. ^ Nisoli E, Tonello C, Landi M, Carruba MO (1996). "Functional studies of the first selective β3-adrenergic receptor antagonist SR 59230A in rat brown adipocytes". Mol. Pharmacol. 49 (1): 7–14. PMID 8569714. 
  5. ^ english
  6. ^ 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. 
  7. ^ 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. PMC 1433140. PMID 2889649. 
  8. ^ 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. 
  9. ^ Circulation & Lung Physiology I M.A.S.T.E.R. Learning Program, UC Davis School of Medicine
  10. ^ Moro, C; Tajouri, L; Chess-Williams, R (January 2013). "Adrenoceptor function and expression in bladder urothelium and lamina propria". Urology. 81 (1): 211.e1–7. doi:10.1016/j.urology.2012.09.011. PMID 23200975. 
  11. ^ a b c d e f Fitzpatrick, David; Purves, Dale; Augustine, George (2004). "Table 20:2". Neuroscience (Third ed.). Sunderland, Mass: Sinauer. ISBN 0-87893-725-0. 
  12. ^ Zhao, T. J.; Sakata, I.; Li, R. L.; Liang, G.; Richardson, J. A.; Brown, M. S. et al. et al. (2010). "Ghrelin secretion stimulated by {beta}1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice". Proc Natl Acad Sci U S A 107 (36): 15868–15873. Bibcode:2010PNAS..10715868Z. doi:10.1073/pnas.1011116107. PMID 20713709. 
  13. ^ Large V, Hellström L, Reynisdottir S et al. (December 1997). "Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function". J. Clin. Invest. 100 (12): 3005–13. doi:10.1172/JCI119854. PMC 508512. PMID 9399946. 
  14. ^ Kline WO, Panaro FJ, Yang H, Bodine SC (February 2007). "Rapamycin inhibits the growth and muscle-sparing effects of clenbuterol". J. Appl. Physiol. 102 (2): 740–7. doi:10.1152/japplphysiol.00873.2006. PMID 17068216. 
  15. ^ Kamalakkannan G, Petrilli CM, George I et al. (April 2008). "Clenbuterol increases lean muscle mass but not endurance in patients with chronic heart failure". J. Heart Lung Transplant. 27 (4): 457–61. doi:10.1016/j.healun.2008.01.013. PMID 18374884. 
  16. ^ Elenkov, I. J., R. L. Wilder et al. (2000). "The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system". Pharmacol Rev 52 (4): 595–638. PMID 11121511. 

Further reading[edit]

  • Rang HP, Dale MM, Ritter JM, Moore PK (2003). "Chapter 11: Noradrenergic transmission". Pharmacology (5th ed.). Elsevier Churchill Livingstone. ISBN 0-443-07145-4. 
  • Rang HP, Dale MM, Ritter JM, Flower RJ (2007). "Chapter 11: Noradrenergic transmission". Rang and Dale's Pharmacology (6th ed.). Elsevier Churchill Livingstone. pp. 169–170. ISBN 0-443-06911-5. 

External links[edit]