Transformation and actions of extracellular NADP⁺ in the rat liver

The possible actions and transformation of extracellular NADP⁺ in the rat liver have not yet been studied. Considering the various effects of its analogue NAD⁺ in the liver, however, effects of NADP⁺ can equally be expected. In the present work, this question was approached in the isolated perfused rat liver to get a preliminary picture of the action of extracellular NADP⁺ in this organ. NADP⁺ (100 μM) produced transient increases in the portal perfusion pressure. Glucose release (glycogenolysis) and lactate production from endogenous glycogen were transiently increased in antegrade and retrograde perfusion. Oxygen uptake was stimulated after a transient inhibition in antegrade perfusion, which was practically absent in retrograde perfusion. Pyruvate production was transiently inhibited. In the absence of Ca²⁺, all of these effects were no longer observed. Bromophenacyl bromide, an inhibitor of eicosanoid synthesis, almost abolished all effects. Suramin, a non-specific purinergic P2YX antagonist, also inhibited the action of NADP⁺. Single pass transformation of 75 μM NADP⁺ was equal to 92%. Besides nicotinamide, at least two additional transformation products were detected: 2'-phospho-ADP-ribose and a non-identified component, the former being more important (67% of the transformed NADP⁺). Nicotinic acid adenine dinucleotide phosphate (NAADP) was not found in the outflowing perfusate. It was concluded that NADP⁺, like NAD⁺, acts on perfusion pressure and glycogen catabolism in the liver mainly via eicosanoid synthesis mediated by purinergic P2YX receptors.