The action of extracellular NAD+ on Ca2+ efflux, hemodynamics and some metabolic parameters in the isolated perfused rat liver.

The action of NAD+ on hemodynamics and metabolism of the isolated perfused rat liver was investigated. Extracellular NAD+ (20-100 microM) stimulated glycogen breakdown (glucose release) and inhibited oxygen uptake. Lactate production was predominantly increased, and pyruvate production was predominantly inhibited. NAD+ also increased the portal perfusion pressure. All metabolic effects were strictly Ca2+-dependent. The effects were absent when Ca2+ was excluded, and reintroduction of the cation restored the effects. In preloaded livers, NAD+ accelerated 45Ca2+ efflux. The action of NAD+ was sensitive to three inhibitors of eicosanoid synthesis, suggesting that this action is mediated by these compounds, which are known to be produced and released by Kupffer and endothelial cells. It is impossible to infer from the available data if NAD+ exerts all these effects by itself or if they are caused by one or more of its extracellular hydrolysis products. Nicotinamide was ineffective and can be excluded, but especially cyclic ADP-ribose and ADP-ribose are possibilities that should be considered in future work.