The role of cyclic-adenosine monophosphate (cAMP) and calcium (Ca2+) in the metabolic responses to adenosine was studied in isolated hepatocytes from fed rats. In the presence of 1.2 mM Ca but not in the absence of Ca2+, adenosine stimulated ureagenesis without increasing cAMP. Adenosine inhibited the glucagon mediated increase in cAMP. Adenosine increased free cytoplasmic Ca2+ provided that cells were incubated in the presence of external Ca2+. In the absence of added Ca2+ adenosine did not stimulate ureagenesis or the movements of Ca2+. It is suggested that, in the liver cell, Ca2+ may be a second messenger for adenosine.
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