The rate of thermal inactivation of the unliganded human Ah receptor,
studied by sucrose density gradient centrifugation, with respect to lo
ss of ligand binding ability, was found to be greater than those of mo
st rodents at 20 degrees C, but the temperature coefficient of the rat
e constant was much smaller than for the rodent species. This implies
that the unliganded human Ah receptor would be thermally more stable t
han the rodent analogs at physiological temperatures. The liganded for
m of the human Ah receptor was found to be less stable with respect to
ligand release than the rodent receptors. These differences in behavi
or between human and rodent Ah receptors underline the difficulties in
using rodent data in the development of receptor-based models of diox
in toxicity. Attempts to develop an alternative to sucrose density gra
dient centrifugation, comparable with the hydroxylapatite adsorption m
ethod used to assay rodent hepatic Ah receptor, were unsuccessful.