alpha-Fluoromethylhistidine-induced inhibition of brain histidine decarboxylase. Implications for the CO2-trapping enzymatic method.
The actions of S-alpha-fluoromethylhistidine (FMH), an irreversible inhibitor 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 complete inhibition of HD in the hypothalamus both in vivo and in vitro. In the frontal cortex, however, maximal doses of FMH did not maximally inhibit HD, suggesting the existence of an FMH-resistant form of HD. Careful studies of the conditions under which the assays were performed (homogenate dilution, preincubation times, incubation times, temperatures), as well as experiments with inhibitors of other decarboxylases, were unable to provide an explanation for this. When comparable studies of the effects of FMH in these brain regions were performed by alternative methods for measuring HD activity, no evidence for the existence of an FMH-resistant form of HD could be found. Thus, even though the CO2-trapping method appears to be accurate for measuring HD activity in rat hypothalamic homogenates, the present results show that this method may not be specific when studying brain regions other than the hypothalamus.
Skratt
J J
JJ
Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.
Hough
L B
LB
Nalwalk
J W
JW
Barke
K E
KE
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002245:Carbon Dioxide / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000201:enzymology; D006632:Histamine / Q000032:analysis; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D007031:Hypothalamus / Q000201:enzymology; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014316:Tritium
D008762:Methylhistidines; D014316:Tritium; D002245:Carbon Dioxide; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase