[Vasoconstrictor effect of uridine triphosphate on pancreatic vascular bed]

Purinoceptors have been classified according to their sensitivity to structural analogues of purines. In addition to the well established and widely distributed P2 purinoceptor subtypes (P2X and P2Y), the existence of "pyrimidine" or "nucleotide" receptors was proposed, which are sensitive to the pyrimidine nucleotide, uridine triphosphate (UTP). Recently, this class of receptor has been included in the P2 purinoceptor classification as a P2U subtype. We have previously shown that pancreatic vascular resistance was modulated by the activation of P2Y and P2X purinoceptors, inducing vasodilation and vasoconstriction respectively. In this study, we investigated the effect of pyrimidine nucleotides on pancreatic vessels. The experiments were performed on isolated rat pancreas perfused at a constant pressure, which was selected to obtain a stable flow rate of 2.5 ml/min before drug administration; thus, any change in pancreatic vascular resistance resulted in a change in the flow rate. UTP induced a decrease in the flow rate at all concentrations tested, but the kinetics differed according to the concentration. The lowest concentration used (16.5 microM) induced a delayed, progressive and long lasting vasoconstriction. Ten times and one hundred times higher concentrations (165 and 1,650 microM) induced an immediate, more pronounced and also long lasting vasoconstriction. In contrast, the other pyrimidine nucleotide cytosine triphosphate (16.5 and 165 microM) did not significantly modify the pancreatic flow rate. This study suggests the presence of a P2U purinoceptor on rat pancreatic vessels; this P2U receptor differs from the P2X receptor since the activation of this latter elicits only a transient vasoconstriction.