Effects of adenosine, adenosine triphosphate and structural analogues on glucagon secretion from the perfused pancreas of rat in vitro

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Abstract
1 The effects of adenosine, adenosine triphosphate (ATP) and structural analogues have been studied on glucagon secretion from the isolated perfused pancreas of the rat in the presence of glucose (2.8 mM). 2 Adenosine induced a transient increase of glucagon secretion. This effect was concentration-dependent in the range of 0.165 to 165 μM. ATP also induced an increase, but the effect was no greater at 165 μM than at 16.5 μM. 3 2-Chloroadenosine, an analogue more resistant to metabolism or uptake systems than adenosine, was more effective. Among the three structural analogues of ATP or ADP studied, β,γ-methylene ATP which can be hydrolyzed into AMP and adenosine had an effect similar to adenosine or ATP at the same concentrations (1.65 and 16.5 μM); in contrast α,β-methylene ATP and α,β-methylene ADP (resistant to hydrolysis into AMP and adenosine) were ineffective. 4 Theophylline (50 μM) a specific blocker of the adenosine receptor, suppressed the glucagon peak induced by adenosine, 2-chloroadenosine, ATP and β,γ-methylene ATP (1.65 μM). 5 An inhibitor of 5′ nucleotidase, α,β-methylene ADP (16.5 μM), reduced the glucagon increase induced by ATP and did not affect the response to adenosine (1.65 μM). 6 These results support the hypothesis of adenosine receptors (P1-purinoceptors) on the pancreatic glucagon secretory cells and indicate that ATP acts after hydrolysis to adenosine.