Overview:α2-Adrenoceptors (nomenclature as agreed by NC-IUPHAR Subcommittee on Adrenoceptors; Bylund et al., 1994) are 7TM receptors, activated by endogenous agonists with a relative potency of adrenaline > noradrenaline. UK14304 (brimonidine) and BHT920 are agonists selective for α2-adrenoceptors relative to α1-adrenoceptors. Rauwolscine (9.0) and yohimbine (9.0) are antagonists selective for α2-adrenoceptors relative to α1-adrenoceptors. [3H]-Rauwolscine (1 nM), [3H]-UK14304 (5 nM) and [3H]-RX821002 (0.5 nM and 0.1 nM at α2C) are relatively selective radioligands. There is species variation in the pharmacology of the α2A-adrenoceptor; for example, yohimbine, rauwolscine and oxymetazoline have an ∼20-fold lower affinity for rat, mouse and bovine α2A-adrenoceptors compared with the human receptor. These α2A orthologues are sometimes referred to as α2D-adrenoceptors. Multiple mutations of α2-adrenoceptors have been described, some of which are associated with alterations in function.
| Nomenclature | α2A | α2B | α2C |
| Other names | α2D | – | – |
| Ensembl ID | ENSG00000150594 | ENSG00000181210 | ENSG00000184160 |
| Principal transduction | Gi/o | Gi/o | Gi/o |
| Selective agonists | Oxymetazoline | – | – |
| Selective antagonists | BRL44408 (8.0) | ARC239 (8.0), prazosin (7.5), imiloxan (7.3) | ARC239 (8.0), prazosin (7.5) |
The effects of classical (not subtype selective) α2-adrenoceptor agonists such as clonidine, guanabenz and brimonidine (UK14304) on central baroreflex control (hyoptension; bradycardia), hypnotic, analgesic, seizure modulation and platelet aggregation are mediated by α2A-adrenoceptors. The roles of α2B- and α2C-adrenoceptors are less clear but the α2B subtype appears to be involved in neurotransmission in the spinal cord and α2C in regulating catecholamine release from adrenal chromaffin cells. Oxymetazoline is a reduced efficacy agonist. Binding sites for imidazolines, distinct from α2-adrenoceptors, have been identified and classified as I1, I2 and I3 sites, but with a function other than coupling to G proteins; catecholamines have a low affinity for these sites.
Glossary
Abbreviations:
- ARC239
2-(2,4-[O-methoxyphenyl]-piperazin)-1-yl
- BHT920
6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine
- BRL44408
2-(2H-[1-methyl-1,3-dihydroisoindole]methyl)-4,5-dihydroimidazole
- MK912
(2S,12bS)1′,3′-dimethylspiro(1,3,4,5′,6,6′,7,12b-octahydro-2H-benzo[b]furo[2,3-a]quinolizine)-2,4′-pyrimidin-2′-one
- RX821002
2-(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline
- UK14304
5-bromo-6-[2-imidazolin-2-ylamino]quinoxaline, also known as brimonidine
Further Reading
Bylund DB, Eikenberg DC, Hieble JP, Langer SZ, Lefkowitz RJ, Minneman KP et al. (1994). International Union of Pharmacology IV. Nomenclature of adrenoceptors. Pharmacol Rev46: 121–136.
Guimaraes S, Moura D (2001). Vascular adrenoceptors: an update. Pharmacol Rev53: 319–356.
Hein L (2006). Adrenoceptors and signal transduction in neurons. Cell Tissue Res326: 541–551.
Kable JW, Murrin LC, Bylund DB (2000). In vivo gene modification elucidates subtype-specific functions of α2-adrenergic receptors. J Pharmacol Exp Ther293: 1–7.
Knaus AE, Muthig V, Schickinger S, Moura E, Beetz N, Gilsbach R et al. (2007). α2-adrenoceptor subtypes – unexpected functions for receptors and ligands derived from gene-targeted mouse models. Neurochem Int51: 277–281.
Koch WJ, Lefkowitz RJ, Rockman HA (2000). Functional consequences of altering myocardial adrenergic receptor signaling. Annu Rev Physiol62: 237–260.
Philipp M, Hein L (2004). Adrenergic receptor knockout mice: distinct functions of 9 receptor subtypes. Pharmacol Ther101: 65–74.
Philipp M, Brede M, Hein L (2002). Physiological significance of α2-adrenergic receptor subtype diversity: one receptor is not enough. Am J Physiol Regul Integr Comp Physiol283: R287–R295.