ALPHA-FLUOROMETHYLHISTIDINE-INDUCED INHIBITION OF BRAIN HISTIDINE-DECARBOXYLASE - IMPLICATIONS FOR THE CO2-TRAPPING ENZYMATIC METHOD

The actions of S-alpha-fluoromethylhistidine (FMH), an irreversible in hibitor of the histamine biosynthetic enzyme histidine decarboxylase ( HD), were studied on rat brain HD, as measured by a recently developed CO2-trapping enzymatic method. As expected, FMH induced a virtually c omplete inhibition of HD in the hypothalamus both in vivo and in vitro . In the frontal cortex, however, maximal doses of FMH did not maximal ly inhibit HD, suggesting the existence of an FMH-resistant form of HD . Careful studies of the conditions under which the assays were perfor med (homogenate dilution, preincubation times, incubation times, tempe ratures), as well as experiments with inhibitors of other decarboxylas es, were unable to provide an explanation for this. When comparable st udies of the effects of FMH in these brain regions were performed by a lternative methods for measuring HD activity, no evidence for the exis tence of an FMH-resistant form of HD could be found. Thus, even though the CO2-trapping method appears to be accurate for measuring HD activ ity in rat hypothalamic homogenates, the present results show that thi s method may not be specific when studying brain regions other than th e hypothalamus.