Adrenergic Receptors

Abstract

Adrenergic receptors are cell‐surface receptors for two major catecholamine hormones and neurotransmitters that regulate key physiological responses, including cardiovascular and pulmonary functions. Operating via heterotrimeric G proteins, adrenergic receptors constitute one of the most intensely studied classes of membrane proteins, whose expression and function are subject to regulation at many different levels, including transcriptional, posttranscriptional and posttranslational.

Keywords: adrenergic receptors; α‐adrenergic receptors; β‐adrenergic receptors; desensitization; downregulation

Figure 1.

Schematic illustration of the topology of adrenergic receptors based upon information gleaned from studies of the β2‐AR. The N‐terminus is extracellular; there are seven (I–VII) transmembrane‐spanning domains with α‐helical character that create three i loops (i loop 1, 2 and 3), and the C‐terminus is cytoplasmic. The region of i loop 3 highlighted in blue is implicated in signalling from receptor to G protein.

Figure 2.

Counterregulation by growth factor receptor tyrosine kinases and homologous desensitization by GRKs share many similarities in receptor phosphorylation, use of accessory proteins and sequestration of the receptors.

Figure 3.

Counterregulation by growth factor receptor tyrosine kinases and homologous desensitization by GRKs both stimulate the sequestration of β2‐AR. An autofluorescent fusion protein of the β2‐AR was created with the green fluorescent protein and then expressed in cells in culture. An optical section of the fluorescent receptors is obtained by epifluorescence confocal microscopy from insulin‐treated (a), untreated (b) and β‐adrenergic agonist‐treated (c) cells. The corresponding phase‐contrast images of the cells are shown in (d)–(f).

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References

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Further Reading

Ballestros J and Palczewski K (2001) G protein‐coupled receptor drug discovery: implications from the crystal structure of rhodopsin. Current Opinions in Drug Discovery & Development 4: 561–574.

Daaka Y, Luttrell LM and Lefkowitz RJ (1997) Switching of the coupling of the beta2‐adrenergic receptor to different G proteins by protein kinase A. Nature 390: 88–91.

Lefkowitz RJ (1998) G protein‐coupled receptors. III. New roles for receptor kinases and beta‐arrestins in receptor signalling and desensitization [Review]. Journal of Biological Chemistry 273: 18677–18680.

Malbon CC, Tao J and Wang HY (2004) AKAPs and molecules that compose their GPCR signalling complexes. Biochemical Journal 379: 1–9.

Petrofski JA and Koch WJ (2003) The beta‐adrenergic receptor kinase in heart failure. Journal of Molecular & Cellular Cardiology 35: 1167–1174.

Qanbar R and Bouvier M (2003) Role of Palmitoylation/depalmitoylation reactions in G‐protein‐coupled receptor function. Pharmacology & Therapeutics 97: 1–33.

Xiang Y and Kobilka BK (2003) Myocyte adrenoceptor signalling pathways. Science 300: 1530–1532.

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Malbon, Craig C, and Wang, Hsien‐yu(Sep 2005) Adrenergic Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0004072]