Path breaking research was carried out by Sutherland on second messenger systems involving the mode of information transmission by epinephrine to target cells in the liver. Sutherland found that epinephrine did not cross the plasma membrane. Instead, epinephrine binds to a receptor molecule in the target cell membrane, initiating a chain of processes that eventuate in catalyzing an increased production of cyclic AMP (cAMP, cyclic adenosine monophosphate) from ATP. A small amount of bound hormone can result in a large increase of cAMP levels in the cell. Higher cAMP levels activate protein kinase A which in turn activates glycogen phosphorylase, the enzyme which cleaves glycogen. The higher cAMP levels also inactivate glycogen synthetase.

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