PR00559

ADRENRGCA2BR

PRINTS entry
Member databasePRINTS
PRINTS typefamily
Short nameADRENRGCA2BR

Description
Imported from IPR000207

The adrenoceptors (or adrenergic receptors) are rhodopsin-like 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, effect blood pressure, myocardial contractile rate and force, airway reactivity, and a variety of metabolic and central nervous system functions. The clinical uses of adrenergic compounds are vast. Agonists and antagonists interacting with adrenoceptors have proved useful in the treatment of a variety of diseases, including hypertension, angina pectoris, congestive heart failure, asthma, depression, benign prostatic hypertrophy, and glaucoma. These drugs are also useful in several other therapeutic situations including shock, premature labour and opioid withdrawal, and as adjuncts to general anaesthetics.

There are three classes of adrenoceptors, based on their sequence similarity, receptor pharmacology and signalling mechanisms
[4]
. These three classes are alpha 1 (a Gq coupled receptor), alpha 2 (a Gi coupled receptor) and beta (a Gs coupled receptor), and each can be further divided into subtypes
[13]
. The different subtypes can coexist in some tissues, but one subtype normally predominates.

There are three subtpyes of alpha 2 adrenoceptors (2A-C). The receptors are usually found presynaptically, where they inhibit the release of noradrenaline, and thus serve as an important receptor in the negative feedback control of noradrenaline release
[9, 10, 12, 11]
. Postsynaptic alpha 2 receptors are located on liver cells, platelets, and the smooth muscle of blood vessels. Activation of the receptors causes platelet aggregation
[6]
, blood vessel constriction
[2, 3]
and constriction of vascular smooth muscle
[8]
. Agonists of alpha 2 adrenergic receptors are frequently used in veterinary anaesthesia, where they affect sedation, muscle relaxation and analgesia through their effects on the CNS
[7]
. Alpha 2 adrenoceptors are coupled through the Gi/Go mechanism, inhibiting adenylate cyclase activity and downregulating cAMP formation.

This entry represents the alpha 2B receptor. It is found in the kidney, brain, and spinal cord, along with the other alpha 2 subtypes. However, it is the only subtype to be found in the heart and liver. Peripheral tissues, predominantly express the alpha 2A and 2B subtypes, with little alpha 2C. This is in contrast to the CNS, where alpha 2A and 2C are predominantly expressed, with little alpha 2B
[1, 5]
.

References
Imported from IPR000207

1.Expression of alpha 2-adrenergic receptor genes in rat tissues. Blaxall HS, Hass NA, Bylund DB. Receptor 4, 191-9, (1994). PMID: 7812219

2.Coronary vasoconstriction mediated by alpha 1- and alpha 2-adrenoceptors in conscious dogs. Woodman OL, Vatner SF. Am. J. Physiol. 253, H388-93, (1987). PMID: 2887122

3.Alpha-adrenoceptors in equine digital veins: evidence for the presence of both alpha1 and alpha2-receptors mediating vasoconstriction. Elliott J. J. Vet. Pharmacol. Ther. 20, 308-17, (1997). View articlePMID: 9280371

4.A study of the adrenotropic receptors. AHLQUIST RP. Am. J. Physiol. 153, 586-600, (1948). PMID: 18882199

5.Initial observations on the localization of mRNA for alpha and beta adrenergic receptors in brain and peripheral tissues of rat using in situ hybridization. Nicholas AP, Pieribone VA, Elde R, Hokfelt T. Mol. Cell. Neurosci. 2, 344-50, (1991). PMID: 19912818

6.Platelet aggregation induced by alpha 2-adrenoceptor and protein kinase C activation. A novel synergism. Siess W, Lapetina EG. Biochem. J. 263, 377-85, (1989). PMID: 2574568

7.alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Khan ZP, Ferguson CN, Jones RM. Anaesthesia 54, 146-65, (1999). View articlePMID: 10215710

8.Cardiovascular regulation in mice lacking alpha2-adrenergic receptor subtypes b and c. Link RE, Desai K, Hein L, Stevens ME, Chruscinski A, Bernstein D, Barsh GS, Kobilka BK. Science 273, 803-5, (1996). View articlePMID: 8670422

9.alpha2-Adrenoceptor agonists: shedding light on neuroprotection? Ma D, Rajakumaraswamy N, Maze M. Br. Med. Bull. 71, 77-92, (2004). View articlePMID: 15684247

10.Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated [35S]GTPgammaS binding. Jasper JR, Lesnick JD, Chang LK, Yamanishi SS, Chang TK, Hsu SA, Daunt DA, Bonhaus DW, Eglen RM. Biochem. Pharmacol. 55, 1035-43, (1998). View articlePMID: 9605427

11.Modulation of agonist binding to recombinant human alpha2-adrenoceptors by sodium ions. Pihlavisto M, Sjoholm B, Scheinin M, Wurster S. Biochim. Biophys. Acta 1448, 135-46, (1998). View articlePMID: 9824686

12.Subtype-specific stimulation of [35S]GTPgammaS binding by recombinant alpha2-adrenoceptors. Peltonen JM, Pihlavisto M, Scheinin M. Eur. J. Pharmacol. 355, 275-9, (1998). View articlePMID: 9760042

13.Subtypes of alpha 2-adrenoceptors: pharmacological and molecular biological evidence converge. Bylund DB. Trends Pharmacol. Sci. 9, 356-61, (1988). View articlePMID: 2855960

Supplementary References

1. G protein involvement in receptor-effector coupling. Casey PJ, Gilman AG. J. Biol. Chem. 263, 2577-80, (1988). View articlePMID: 2830256

2. Design of a discriminating fingerprint for G-protein-coupled receptors. Attwood TK, Findlay JB. Protein Eng. 6, 167-76, (1993). View articlePMID: 8386361

3. Fingerprinting G-protein-coupled receptors. Attwood TK, Findlay JB. Protein Eng. 7, 195-203, (1994). View articlePMID: 8170923

4. G proteins in signal transduction. Birnbaumer L. Annu. Rev. Pharmacol. Toxicol. 30, 675-705, (1990). View articlePMID: 2111655

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