The changes in flow rate in the isolated pancreas of the rat in response to natural purine nucleotides and phosphate-modified analogues were recorded. ATP and ADP transiently decreased the flow rate in a dose-dependent manner but only at very high concentrations (greater than 165 microM). In contrast, alpha,beta-methylene ATP, the most active of the drugs used, decreased the flow rate of the preparation at very low concentrations: 0.495 microM induced about 50% of the maximum effect. beta, gamma-Methylene ATP and AMP-PNP had an intermediary potency. Pyrophosphate had no effect. AMP and adenosine had no vasoconstrictor effect even at 1650 microM. The vasoconstrictor effect of alpha,beta-methylene ATP was not antagonized by phenoxybenzamine (6 microM) or by apamin (0.01 microM). In contrast PIT, a P2-purinergic receptor antagonist, partially or totally blocked the alpha,beta-methylene ATP effect depending on the concentrations used. From our results it can be concluded that purinergic receptors of P2-type are present on the vascular smooth muscle of the pancreatic bed in the rat.
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