Cytochrome P-450 monooxygenase system in the rabbit kidney: its intranephron localization and its induction.
Two components of the renal cytochrome P-450 (P-450) monooxygenase system, P-450 and NADPH-cytochrome c (cyt. c) reductase, were estimated using rabbit kidney slices and isolated nephron segments. Renal P-450 was distributed in the mitochondrial and microsomal fractions of both slices and nephron segments. P-450 (mitochondrial plus microsomal) was localized exclusively in the proximal tubule, with the highest activity in the S2 portion (18.14 +/- 5.47 fmoles/mm, 134.4 fmoles/micrograms protein). Intraperitoneal injection of 3,4-benzo(a)pyrene (BP) induced a 2-fold increase of only the microsomal P-450. The intraproximal site of BP action was localized in a definite portion, a segment 3 to 6 mm distant from the glomerulus (49.0 +/- 7.7 to 103.9 +/- 3.5 fmoles/micrograms protein), suggesting that inducible P-450 molecules may be enriched in this portion. Multiplicity of renal P-450 could be demonstrated electrophoretically. Comparison of the pattern from BP treated rabbits with control hemeprotein indicated that BP induced a higher molecular weight P-450. The highest concentrations of NADPH-cyt. c reductase were distributed in the cortical microsomes, although it was also detectable in the papilla. The reductase was distributed along the entire single nephron, with highest concentrations in the S2 portion of the proximal tubule. In conclusion, the P-450 monooxygenase system is localized in the proximal tubule and in the control condition, the highest activity is found in the S2 portion.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D007668:Kidney / Q000201:enzymology*; D007687:Kidney Tubules, Proximal / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009399:Nephrons / Q000201:enzymology; D010105:Oxygenases / Q000096:biosynthesis / Q000378:metabolism*; D011817:Rabbits
D001580:Benzopyrenes; D002273:Carcinogens; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase