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) [20], e.g. adrenoceptors, muscarinic cholinergic receptors , rhodopsin   and the receptors for the antidiuretic hormone. These receptors show certain similarities concerning their molecular structure [21, 22] (see section genetics). 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 and adrenoceptors share 54% of their sequence. The extracellular N-terminus contains several N-glycosylation sites , the inner loop CIII and the C-terminus carry phosphorylation sites   (see figure figrecstruct). 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   [22], such as the , [23, 24] types of -receptors or the , , , , [25, 26, 27, 28, 29, 30, 31, 32] and types of the -receptor. Recently a -receptor of the fatty tissue (termed adrenoceptor) lacking phosphorylation sites was discovered[33]  . All these subtypes can readily be divided into three groups by their molecular biological characteristics.

-receptors:

binding G protein, activating inositole triphosphate and diacylglycerole as second messengers,

-receptors:

binding the inhibitory G protein, restraining the adenylcylase system, cAMP   as second messenger,

-receptors:

binding the adenylate cyclase stimulating G protein, cAMP as second messenger.

The human adrenoceptor subtypes are located on distinct genloci , which happen to be rather close for and as well as and (see table 1.3).  

 
Table 1.3: Genloci of various adrenergic receptor subtypes