INHIBITION OF p-AMINOHIPPURATE TRANSPORT BY CYCLIC GMP IN RAT KIDNEY CORTICAL SLICES

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The effect of cyclic GMP on the accumulation of p-aminohippurate (PAH) was investigated by using rat kidney corrical slices. When the slices were preincubated with cyclic GMP and thereafter incubated in the absence of the cyclic nucleotide for the assay of PAH transport, cyclic GMP inhibited PAH accumulation in the slices in a dose-dependent fashion. Pretreatment of the slices with dibutyryl cyclic GMP induced no inhibition of PAH uptake, but that with the combination of cyclic GMP and butyrate inhibited the accumulation to the same extent as did cyclic GMP. Guanosine and its monophsphate (GMP) had no effect on PAH accumulation in the slices. Inhibitory effect of cyclic GMP on PAH accumulation was not due to the changes of electrolyte content and water distribution in the slices. The slices pretreated with cyclic GMP at 0℃ failed to decrease PAH accumulation. Cyclic GMP had no effect on organic cation (tetraethylammonium, TEA) transport in the slices. These evidence suggest that cyclic GMP may be able to modulate the rat renal transport system for PAH although this study does not explain the mechanism of inhibition of PAH transport by the cyclic nucleotide.
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