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Functionality

  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).

  table320
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: tex2html_wrap_inline4793 (39-52kDa), tex2html_wrap_inline4771 (35-36kDa) and tex2html_wrap_inline5013 (8-10kDa). The sequence of events leading to signal transduction by the tex2html_wrap_inline4773 -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 tex2html_wrap_inline4793 -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 tex2html_wrap_inline4793 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.



Alexander Binder
Wed Jan 15 03:01:31 MET 1997