As mentioned above, the 2ar is linked to a guanine nucleotide regulatory protein. Several types of these proteins have been described[21] (see table tab:g-table).
Table 1.4: Guanine Nucleotide Binding Protein Classes
The G-proteins are located at the cytoplasmic side of the cell membrane and consist of three subunits: (39-52kDa), (35-36kDa) and (8-10kDa). The sequence of events leading to signal transduction by the -adrenergic receptor can be described as follows[21, 20, 34]:
The binding of an agonist to the binding domain of the receptor is followed by binding of the receptor to the -subunit of the G protein. As a consequence the G protein is activated (substitution of GTP for GDP) and the receptor is phosphorylated by a specific kinase. This phosphorylated receptor dissociates from the cell membrane and translocates into the cell. The G protein dissociates to its subunits. The subunit, now bound to GTP, stimulates the adenylate cyclase which is located at the cytoplasmic side of the cell membrane, resulting in a plasmatical cAMP concentration rise. The G protein can also interfere in ion channel regulation. The bound GTP is converted to GDP and inactivates the G protein. The activity of the adenylate cyclase decays. The receptor is dephosphorylated and re-enters the cell membrane, eventually completing the cycle. In stage this the receptor can again react with a ligand.
The cAMP acts as second messenger: by activating protein kinases which in turn phosphorylate various proteins. The specific cell response is determined by these phosphorylated proteins and the protein kinases being present.