Cellular distribution of cytochromes P-450 in the rat kidney

The distribution of several cytochrome P-450 (P-450) isoenzymes between pro ximal tubular (PT) and distal tubular (DT) cells of the rat kidney was dete rmined. Western blot analysis of microsomes prepared from liver and kidney cortical homogenates revealed that CYP2E1 protein was expressed in rat kidn ey microsomes at approximately 10% of hepatic levels. Microsomes from renal cortical, PT, and DT cells all expressed CYP2E1, with DT microsomes expres sing slightly higher levels than PT microsomes. In contrast, chlorzoxarone hydroxylation activity was markedly higher in microsomes from PT cells than in those from DT cells. Northern blot analysis of total RNA from PT and DT cells exhibited a pattern of CYP2E1 mRNA distribution similar to that of C YP2E1 protein. CYP2C11 protein expression in renal cortical microsomes was approximately 10% of that in liver microsomes but was significantly higher in microsomes from Pi cells than in those from DT cells. CYP3A1/2 was not d etected in microsomes from either cortical, PT, or DT cells, but was detect ed in microsomes isolated from total liver or kidney cortical homogenates. CYP2B1/2 expression was detected in all tissues tested. The peroxisomal pro liferator clofibrate enhanced the level of CYP2B1/2 in microsomes from both total liver and kidney cortical homogenates but not in microsomes from cor tical, PT, or DT cells, CYP4A2/3 protein and CYP4A mRNA expression were det ected in microsomes from total liver and kidney cortical homogenates and fr om renal cortical, PT, and DT cells using Western and Northern blot analyse s, respectively. Lauric acid hydroxylation activity, an indicator of CYP4A, was comparable in PT and DT cells. Clofibrate elevation of CYP4A in cortic al, PT, and DT microsomes was not as great as that detected in total kidney cortical microsomes, These results establish the distribution of several P -450 isoenzymes between different cell populations of the rat kidney. Furth ermore, these results present evidence that the level of induction of certa in P-450 isoenzymes in the kidney is cell type-specific.