The general objective of the project is to accurately describe the adenosine transduction mechanism in the regulation of liver metabolism.
Specific objectives:
The participation of adenosine in the regulation of different aspects of cell life has recently been described. There is abundant information to this respect in the case of the central nervous system where adenosine functions as neurotransmitters do. Our group is the pioneer in researching the set of metabolic responses recorded in isolated hepatocytes when incubated under adequate conditions in the presence of adenosine. This nucleoside, which is used in concentrations reported in the blood, stimulates ureogenesis (synthesis of urea from ammonium) and gluconeogenesis (synthesis of glucose from lactate) in the isolated hepatocytes. Both effects can also be obtained with non-metabolizable adenosine analogues and it can therefore be concluded that both adenosine metabolic actions depend on the molecule as a whole and not on the products of its degradation. In the case of the nervous system and other tissues, it has been demonstrated that adenosine binds to a membrane receptor and, through a transduction system, a second intracellular messenger is generated that operates as an indispensable link between the adenosine and the cell response; in the case of the nervous system and adenosine, the usual messenger is cyclical adenosine monophosphate (AMPc). By analogy, it can be supposed that the hepatocyte has receptors for adenosine and that the second messenger is AMPc. Our work group has shown that adenosine does not promote changes in the AMPc well and that the second messenger of adenosine is calcium. As a consequence, adenosine promotes an increase in cytosolic calcium, possibly through a specific ion channel for this cation and that, in turn, the change in the cytosolic calcium concentration stimulates ureogenesis and gluconeogenesis.