Influence of papaverine on cyclic nucleotide level and cellular metabolism in rat kidney cortex in terms of its inhibitory effect on p-aminohippurate transport.

Abstract

We attempted to determine whether there is a possible link between the effect of papaverine on p-aminohippurate (PAH) accumulation, on cyclic nucleotide content and on certain other cellular functional parameters in rat kidney cortical slices in vitro. Papaverine at a concentration of 0.1 mM almost completely inhibited PAH accumulation in the slices. However, cyclic guanosine 3', 5'-monophosphate (cyclic GMP) and cyclic adenosine 3', 5'-monophosphate (cyclic AMP) levels in the slices were not significantly affected by papaverine at 0.1 mM, though papaverine at a concentration of 1 mM increased the cyclic GMP level without affecting the cyclic AMP level. Papaverine (0.1 mM) produced a decrease in the sodium gradient and in the adenosine triphosphate (ATP) level in the slices. Calcium uptake by mitochondria, isolated from kidney cortex, was apparently decreased in the presence of 0.1 mM papaverine. These results suggest that the inhibition of phosphodiesterase probably does not explain the action of papaverine on PAH accumulation in the slices. The inhibition of PAH accumulation by papaverine is partly a reflection of the fall in the sodium gradient in the slices treated with papaverine. In addition, a depression of ATP level in the slices and an inhibition of mitochondrial calcium uptake may be related to a possible mechanism of action of papaverine on PAH accumulation.