Uridine nucleotide-induced stimulation of gluconeogenesis in isolated rat proximal tubules

Uridine nucleotides, released into the extracellular environment, influence a variety of metabolic and other cellular activities in a wide range of target tissues. Here we have studied the effects of uridine nucleotides on gluconeogenesis in isolated rat proximal tubules. Gluconeogenesis, from a range of precursors, was stimulated following exposure of isolated proximal tubules to either UTP or UTPgammaS, but not when exposed to other uridine-containing nucleotides. UTP- and UTPgammaS-induced gluconeogenesis was diminished in the presence of purinoceptor antagonists (e.g. suramin, PPADS) indicative of a role for P2Y(2)-like purinoceptors in these effects. Likewise, agents that interfere with either phospholipase C activation or intracellular Ca2+ mobilization decreased UTP- and UTPgammaS-induced stimulation of gluconeogenesis consistent with a role for these secondary messenger systems in the mechanism of action of extracellular UTP and UTPgammaS on proximal tubule metabolism.