1.4.2 The Adrenergic Receptor

A number of receptors transmit signals from the extracellular space to the intracellular compartment by means of a guanine nucleotide binding protein (G-Protein) [71], e.g. adrenoceptors, muscarinic cholinergic receptors, rhodopsin and the receptors for the antidiuretic hormone. These receptors show certain similarities concerning their molecular structure  [72, 73] (see section 1.5). They all possess seven membrane spanning domains, hence they are referred to as seven membrane spanning domain receptors. These hydrophobic domains have a length of 20 to 24 amino acids. The N-terminus of the receptor and three loops are located extracellularly (EI – EIII), the C-terminus and three loops extend intracellularly (CI – CIII). The β₁ and β₂ adrenoceptors share 54% of their sequence. The extracellular N-terminal region contains several N-glycosylation sites, the inner loop CIII and the C-terminus carry phosphorylation sites (Figure 1.5). The membrane crossing sections are ligand binding domains, the intracellular parts are bound to the G-protein. The high variability of the C-III loop and the C-terminus seems to be the main cause of the receptor specific aspects of binding the G-protein.

Molecular biological studies revealed further subtypes of adrenergic receptors  [73], such as the α_1A, α_1B [74, 75] types of α₁-receptors or the α_2A, α_2B, α_2C2, α_2C4, α_2C10  [76, 77, 78, 79, 80, 81, 82, 83] and α_2D types of the α₂-receptor. Recently a β-receptor of the adipose tissue (termed β₃ adrenoceptor) lacking phosphorylation sites was discovered [84] .

The adrenoceptors share considerable amino acid sequence identity. The transmembrane-spanning domains (TMDs) show the highest homology, followed by the first two cytoplasmic loops. The third cytoplasmic loop and the amino and carboxyl termini are most divergent within the adrenoceptor family. The overall homogeneity of β₁- and β₂-receptors is 54%, increasing to 71% between β₁- and β₂-receptors and 69% between β₁- and β₃-receptors in hydrophobic transmembrane regions  [73].

The human adrenoceptor subtypes are located on distinct gene loci, which happen to be rather close for α_1B and β₂ as well as α_2A and β₁ (Table 1.5).

© 2001 Alexander Binder