Isolation of rat intestinal microsomes: partial characterization of mucosal cytochrome P-450

Arch Biochem Biophys. 1986 Feb 1;244(2):492-501. doi: 10.1016/0003-9861(86)90618-1.

Abstract

A procedure is presented for the isolation of subcellular fractions from small intestinal mucosal cells in the rat. The mucosal cells were detached by a scraping procedure resulting in an almost complete harvest of all types of cells as judged by light microscopy. Homogenization using a Potter-Elvehjem Teflon-glass device at high speed with ensuing sonication was found to be necessary for complete disruption of the cells. The subcellular fractions obtained after differential centrifugation--10,000g pellet, 105,000g pellet (microsomal fraction), and supernatant--were characterized with respect to different marker enzymes. The highest yield of 7-ethoxyresorufin-O-deethylase and NADPH-cytochrome c reductase activity in the microsomal fraction was achieved after resuspension and recentrifugation of the 10,000g pellet. Addition of anti-P-450 beta-naphthoflavone (BNF)-B2 antibodies to the incubation mixture resulted in almost complete inhibition of the O-deethylation of 7-ethoxyresorufin whereas addition of anti-P-450 phenobarbital (PB)-B2 had no effect. The presence of BNF-inducible isozymes was demonstrated by the Western blotting technique not only in intestinal microsomes from BNF-treated rats, but also in microsomes from untreated rats. Anti-P-450 BNF-B2 was also used in the peroxidase-antiperoxidase method for studies on the localization of cytochrome P-450. No BNF-inducible cytochrome P-450 could be detected in untreated rats, whereas BNF treatment resulted in a general staining of the whole villus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoflavones / pharmacology
  • Cell Separation / methods*
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 Enzyme System / analysis*
  • Cytochrome P-450 Enzyme System / immunology
  • Female
  • Intestinal Mucosa / enzymology*
  • Intestinal Mucosa / ultrastructure
  • Microsomes / enzymology*
  • NADH Dehydrogenase / analysis
  • Oxidoreductases / analysis
  • Rats
  • Rats, Inbred Strains
  • beta-Naphthoflavone

Substances

  • Benzoflavones
  • beta-Naphthoflavone
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • Cytochrome P-450 CYP1A1
  • NADH Dehydrogenase