RENIN REGULATION IN CULTURED PROXIMAL TUBULAR CELLS

Recent studies have documented the presence of a complete renin-angiot ensin system in the proximal tubule of the kidney; however, little is known about the regulation of renin in this proximal tubular system. T herefore, we performed the present studies to learn whether the behavi or of the renin system in cultured proximal tubule is similar to that of the juxtaglomerular renin system. Basal renin secretion from rabbit proximal tubular cells in primary culture was low and not affected by isoproterenol (10(-5) mol/L), diltiazem (10(-5) mol/L), or a zero-cal cium bath (0 nmol/L). Only the calcium ionophore A23187 (10(-4) mol/L) significantly reduced renin secretion in these cells (from 2.44+/-0.3 7 to 1.14+/-0.08 ng angiotensin I/mg protein per hour, P<.05). When th e proximal tubular cells were lysed so the effects or the test agents on intracellular renin content could be assessed, isoproterenol caused a significant twofold (107%) increase (from 2.02+/-0.56 to 4.18+/-0.8 1 ng angiotensin I/mg protein per hour, P<.05), whereas diltiazem, A23 187, and zero- and high-calcium baths did not produce a significant ch ange. The effects of these agents on renin mRNA were examined in rabbi t and rat proximal tubular cells in primary culture with the use of an S-1 nuclease protection assay. Densitometry analysis of renin mRNA an d either GAPDH mRNA (rat) or alpha-actin (rabbit) showed no significan t alterations in renin mRNA abundance. Ln summary, these results confi rm the presence of renin mRNA in cultured proximal tubular cells and s uggest that a low-level, constitutive secretion of renin occurs in thi s system that is decreased by A23187. Moreover, the results also sugge st that proximal tubular renin is regulated. albeit differently from t he juxtaglomerular renin system. Finally, short-term increments in pro ximal tubular renin occur without a change in renin mRNA.