Adrenergic Receptors

Adrenergic receptors (adrenoceptors) are classified into two main groups, α and β. The α group has been further divided into α1 and α2 which are, in turn, subdivided into α1A, α1B, α1D and α2A, α2B and α2C respectively. β-Adrenoceptors are currently classified into β1, β2 and β3 subgroups with a putative β4 receptor, as yet uncloned but exhibiting a distinct pharmacological profile.

Targets
Literature
Receptor Data

Literature for Adrenergic Receptors

Cardiovascular

Cardiovascular Research Product Guide

A collection of over 250 products for cardiovascular research, the guide includes research tools for the study of:

  • Hypertension
  • Thrombosis and Hemostasis
  • Atherosclerosis
  • Myocardial Infarction
  • Ischemia/Reperfusion Injury
  • Arrhythmias
  • Heart Failure
Cardiovascular

Cardiovascular Poster

Cardiovascular disease remains one of the major causes of morbidity and mortality in the Western world and therefore this therapeutic area continues to be of great interest to researchers. This poster highlights the key GPCRs regulating vascular reactivity.

Depression

Depression Poster

Major depressive disorder is characterized by depressed mood and a loss of interest and/or pleasure. Updated in 2015 this poster highlights presynaptic and postsynaptic targets for the potential treatment of major depressive disorder, as well as outlining the pharmacology of currently approved antidepressant drugs.

α1-Adrenergic Receptor Data

Receptor Subtype α1A α1B α1D
Transduction Mechanism Activates Gp/q, ↑ PI turnover, ↑[Ca2+]i.c., activates voltage-gated Ca2+ channels
Localization CNS, heart, liver, prostate, urethra CNS, somatic arteries and veins, spleen, kidney CNS, aorta, bladder, prostate
Tissue Function Smooth muscle contraction, myocyte hypertrophy, activation of sarcolemmal Na+-H+ exchanger Smooth muscle contraction, cardiac growth and contractile function Smooth muscle contraction
Selective Agonists A 61603 (1052)
Oxymetazoline (1142)
Unknown Unknown
Non-subtype Selective Agonists Cirazoline (0888)
(R)-(-)-Phenylephrine hydrochloride (2838)
Cirazoline (0888)
(R)-(-)-Phenylephrine hydrochloride (2838)
Cirazoline (0888)
(R)-(-)-Phenylephrine hydrochloride (2838)
Selective Antagonists RS 17053 (0985)
RS 100329 (1325)
SNAP 5089 (2398)
WB 4101 (0946)
Tamsulosin (3050)
Rec 15/2615 (3284) BMY 7378 (1006)
Non-subtype Selective Antagonists Prazosin (0623)
Doxazosin (2964)
Alfuzosin (3305)
Prazosin (0623)
Doxazosin (2964)
Alfuzosin (3305)
Prazosin (0623)
Doxazosin (2964)
Alfuzosin (3305)

α2-Adrenergic Receptor Data

Receptor Subtype α2A α2B α2C
Transduction Mechanism Activates Gi/o, ↓ PI turnover, inhibits voltage-gated Ca2+ channels, activates voltage-gated Ca2+ dependent K+ channels
Localization Brain, spleen, kidney, aorta, lung, skeletal muscle, heart, liver Spleen, kidney, aorta, lung, skeletal muscle, heart, liver Brain, kidney, aorta, lung, skeletal muscle, heart, spleen
Tissue Function Hypotension, sedation, analgesia, hypothermia, anesthesia, inhibition of noradrenalin release Vasoconstriction Presynaptic inhibition of noradrenalin release
Selective Agonists Oxymetazoline* (1142)
Guanfacine (1030)
Unknown (R)-(+)-m-Nitrobiphenyline oxalate
ST 91 (2638)
Non-subtype Selective Agonists Clonidine (0690)
UK 14,304 tartrate (2466)
Clonidine (0690)
UK 14,304 tartrate (2466)
Clonidine (0690)
UK 14,304 tartrate (2466)
Selective Antagonists BRL 44408 (1133) ARC (0928)
Imiloxan (0986)
Prazosin (0623)
JP 1302 (2666)
Rauwolscine† (0891)
Non-subtype Selective Antagonists RS 79948 (0987)
Yohimbine (1127)
Efaroxan (0792)
Idazoxan (0793)
RS 79948 (0987)
Yohimbine (1127)
Efaroxan (0792)
Idazoxan (0793)
RS 79948 (0987)
Yohimbine (1127)
Efaroxan (0792)
Idazoxan (0793)
*partial agonist
†10-20 fold selective for α2C

β-Adrenergic Receptor Data

Receptor Subtype β1 β2 β3
Transduction Mechanism ↑ Adenylyl cyclase (via Gs)
Localization CNS, heart, coronary artery, lung, spleen, kidney, liver, muscle CNS, heart, lung, spleen, kidney, liver, skeletal muscle Adipose tissue, gall bladder, small intestines, stomach, prostate, left atrium, bladder, vascular endothelium
Tissue Function Tachycardia, coronary vasodilation, increase heart contractile force, apoptosis, relaxation of colon and esophagus Hypotension, smooth muscle relaxation e.g. bronchodilation, inhibition of apoptosis Lipolysis, glucose uptake, cardioinhibition, relaxation of colon, esophagus and bladder

Key Compounds Ki values (nM)
Agonists BRL 37344 (0948)
CGP 12177* (1134)
Cimaterol (0435)
Pindolol (0994)
Salbutamol (0634)
1750
0.9
-
3.4
-
1120
4
-
2.3
-
287
88
4700
11
53000
Antagonists ICI 118,551 (0821)
L-748,337 (2760)
120
390
1.2
204
257
4

*β3 partial agonist, β1/β2

References

Bylund et al (1994) Pharmacol.Rev. 46 121.Hieble et al (1995) J.Med.Chem. 38 3415. Strosberg and Pietri-Rouxel (1996) TiPS 17 373. Docherty et al (1998) Eur.J.Pharmacol. 361 1. Robinson and Hudson (1998) Tocris Reviews. No. 8.