As mentioned above, the β2 adrenergic receptor is linked to a guanine nucleotide regulatory protein. Several types of these proteins have been described [72] (Table 1.6).
The G-proteins are located at the cytoplasmic side of the cell membrane and consist of three subunits: α (39–52kDa), β (35–36kDa) and γ (8–10kDa). The sequence of events leading to signal transduction by the β2-adrenergic receptor can be described as follows [72, 71, 87]:
After the binding of an agonist to the binding domain of the receptor, this receptor is able to associate with the α subunit of the G-protein, causing the dissociation of GDP from the G-protein. Binding of GTP to the G-protein reduces the affinity of the β agonist and the regulatory unit to the receptor. The receptor is phosphorylated by a specific kinase, and the whole hormone-receptor regulatory unit complex dissociates from the cell membrane and translocates into the cell. The G-protein dissociates to its subunits. The α subunit of the Gs protein, now bound to GTP, stimulates the adenylate cyclase which is located at the cytoplasmic side of the cell membrane, leading to a rise of the cytoplasmatic cAMP concentration. In case of an α2 receptor the Gi protein would inhibit adenylate cyclase which results in a decrease of cytoplasmatic cAMP concentration. The stimulation or inhibition of adenylate cyclase persists until the bound GTP is hydrolysed to GDP by GTPase and inactivates the G protein. The G protein can also interfere in ion channel regulation. The receptor is dephosphorylated and re-enters the cell membrane, eventually completing the cycle. Occupation of the receptor by an agonist again induces the binding of the regulatory unit to the receptor and restarts the process.
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.
© 2001 Alexander Binder