dibutyryl-cyclic-gmp and Hypertrophy

1. Renal cortical slices incubated for 4 hr in culture medium in the presence of either dibutyrylguanosine-3': 5'-cyclic monophosphate (dibutyryl cyclic GMP, 10(-6)m) or freeze-dried normal rat plasma (35 mug mg(-1) wet wt. tissue) did not show any change in dry weight or protein content. However, addition of freeze-dried normal plasma together with dibutyryl cyclic GMP led to an increase in both parameters.2. Unilateral nephrectomy produced a marked increase in the level of arginylesteropeptidase in the renal cortex of the remaining kidney. A similar increase was observed in renal cortical slices incubated with dibutyryl cyclic GMP in vitro.3. The renal cortical esteropeptidase was inhibited by phenylmethylsulphonyl fluoride (PMSF, 2 mm). The inhibitor did not, however, prevent the normal increase of dry weight and protein content of renal cortical slices incubated with plasma from unilaterally nephrectomized rats. Similarly, control normal plasma incubated with cortical slices from a kidney removed 10 min after unilateral nephrectomy became endowed with renotrophic activity (Dicker & Morris, 1980b) but this activation was abolished by PMSF.4. Control plasma treated with a purified arginylesteropeptidase and incubated for 4 hr with renal cortical slices produced a hypertrophy of the slices similar to that evoked by plasma from a unilaterally nephrectomized rat.5. Since following unilateral nephrectomy there is a rapid increase in the level of cyclic GMP in the renal cortical tissue of the remaining kidney (Dicker & Greenbaum, 1977) it is suggested that this increase leads to the induction of a specific arginylesteropeptidase. The possibility that the enzyme then cleaves a renotrophic precursor normally present in the plasma, so converting it to an active form, is discussed.

Topics: Aminopeptidases; Animals; Dibutyryl Cyclic GMP; Hypertrophy; Kidney; Kidney Cortex; Male; Nephrectomy; Rats; Rats, Inbred Strains