Adenosine reduces agonist-induced production of inositol phosphates in rat aorta.

Abstract

In rat aortic strips rendered permeable with digitonin, inositol trisphosphate induced an efflux of 45Ca from the tissue. This release was not affected by adenosine. In tissues not treated with digitonin the contents of inositol trisphosphate (IP3) and its metabolite inositol 1-phosphate (IP1) were significantly enhanced by noradrenaline in the lithium-treated rat aorta. Adenosine was without effect on levels of IP1 or IP3 in tissues which had not been pretreated with noradrenaline, however, the noradrenaline-enhanced tissue content of IP1 was reduced by adenosine in a dose-dependent manner. The reduction in IP1 content by adenosine was enhanced by the uptake blocker dipyridamole (10 microM) and was blocked by the adenosine receptor antagonist 8-phenyltheophylline (10 microM). Adenosine may therefore lower production of inositol phosphates and thus reduce the stimulated release of calcium from intracellular stores. It is proposed that a reduction in phosphatidylinositol turnover may play a role in adenosine-mediated relaxation of blood vessels.