Femoral vascular responses to purine and pyrimidine derivatives: release of 5-hydroxytryptamine by purine derivatives in isolated, cross-circulated rat hindlimb

Abstract

The mode of actions of the purines, adenosine, adenosine-5'-triphosphate (ATP), guanosine and guanosine-5'-triphosphate (GTP), and the pyrimidines, cytidine, cytidine-5'-triphosphate (CTP), thymidine, thymidine-5'-triphosphate (TTP), uridine and uridine-5'-triphosphate (UTP) was investigated in the isolated hindlimb preparation of the rat. A single injection of adenosine, ATP, GTP or UTP into the femoral artery induced a biphasic response, a prominent vasoconstriction preceded by a transient vasodilatation, whereas guanosine and uridine caused only a vasoconstriction. Cytidine, CTP, thymidine and TTP were almost ineffective on the vascular bed. The vasoconstrictor responses to adenosine, ATP, guanosine and GTP were effectively antagonized by either methysergide or reserpine, whereas those to uridine and UTP were not modified by either methysergide or phentolamine. Adenine, D-(-)-ribose and hypoxanthine had no effect on the vascular bed. The 5-hydroxytryptamine (5-HT) release from the hindlimb was fluorometrically determined. The present results provide direct evidence that the vasoconstriction caused by ATP, adenosine, GTP and guanosine is attributed to the release of 5-HT from their stores and that purine nucleotides and nucleosides are capable of releasing 5-HT.