Biochemical quantitation and histochemical localization of carboxylesterase in the nasal passages of the Fischer-344 rat and B6C3F1 mouse

Toxicol Appl Pharmacol. 1987 Apr;88(2):183-94. doi: 10.1016/0041-008x(87)90004-4.

Abstract

Inhalation exposure of rats and mice to glycol ether acetates and acrylate esters causes degeneration of the olfactory epithelium but not of the respiratory epithelium. Since these compounds are metabolized via carboxylesterase to acids that are toxic to the olfactory epithelium, the activity and cellular distribution of carboxylesterase in the nasal passages of rats and mice were studied. Olfactory mucosal carboxylesterase in both rats and mice was found to have a Vmax value for the hydrolysis of p-nitrophenyl butyrate approximately 3 to 6 times larger than that for respiratory mucosa. Similarly, the second-order rate constant for binding and catalysis, V/K, was approximately four times greater in olfactory mucosa than in respiratory mucosa of both rats and mice. These data demonstrate that the olfactory mucosa of rats and mice hydrolyze carboxylesters more efficiently than the respiratory mucosae. Enzyme histochemistry was employed to identify the individual cells within the respiratory and olfactory mucosae which contain carboxylesterase activity. All cell types of the respiratory epithelium had some carboxylesterase activity, with varying intensities between individual cell populations. Ciliated and cuboidal epithelial cells were most active in this region. In the olfactory mucosa, however, Bowman's glands stained most intensely, sustentacular cells demonstrated moderate activity, and no activity was detectable in olfactory sensory cells. Together, these data quantitate carboxylesterase activity in nasal mucosal homogenates and localize the enzyme in individual cell types. The data suggest that olfactory mucosa may metabolize carboxylesters to acids more readily than respiratory mucosa. However, such metabolism does not occur in the target cell population, the olfactory sensory neurons, raising the possibility of intercellular migration of toxic acid metabolites.

MeSH terms

  • Animals
  • Butyrates
  • Carboxylesterase
  • Carboxylic Ester Hydrolases / analysis*
  • Female
  • Histocytochemistry
  • Kinetics
  • Male
  • Mice
  • Nasal Mucosa / enzymology*
  • Olfactory Mucosa / enzymology
  • Rats
  • Rats, Inbred F344
  • Sex Characteristics
  • Species Specificity

Substances

  • Butyrates
  • 4-nitrophenyl butyrate
  • Carboxylic Ester Hydrolases
  • Carboxylesterase