Histidine decarboxylase in rat stomach ECL cells: relationship between enzyme activity and different molecular forms

Mammalian HDC mRNA encodes a protein with a molecular mass of 74 kDa. The r eported molecular mass for the purified HDC subunit is 53-55 kDa. Western b lot analysis of extracts of rat gastric mucosa and fetal rat liver has reve aled the presence of at least three different forms of HDC immunoreactivity , having molecular masses of about 74, 63 and 53 kDa. There is evidence fro m previous studies that full length rat HDC is enzymatically inactive and t hat activation requires C-terminal truncation. In the present study we exam ined the various immunoreactive HDC forms in rat oxyntic mucosa and their r esponse to treatments known to affect the HDC activity. Freely fed rats and hypergastrinemic rats (treated with gastrin or the proton pump inhibitor o meprazole) had higher oxyntic mucosal HDC activity and HDC mRNA level than fasted or untreated rats. The difference in HDC activity was greater than t he difference in HDC mRNA level. Western blot analysis confirmed the existe nce of the 74, 63 and 53 kDa HDC forms in the oxyntic mucosa. All three for ms were more abundant in the oxyntic mucosa of freely fed and hypergastrine mic rats than in the mucosa of fasted or untreated rats. Of the three HDC f orms, the 63 kDa form was the predominant one, the 73 kDa form was quantiat ively insignificant by comparison and the 53 kDa form was at or below the l imit of detection in fasted rats. The activity of HDC was well correlated t o the amount of the 63 kDa HDC form. Administration of cycloheximide to hyp ergastrinemic rats (undergoing omeprazole treatment) resulted in a rapid de cline of the HDC activity (estimated half-life 1 h and 50 min). The 63 kDa HDC form disappeared with a rate that corresponded to the decline in HDC ac tivity. The two other HDC forms seemed to have a slower turnover. Our findi ngs suggest that the 63 kDa form is enzymatically active. The results do no t allow any conclusion as to the functional activity of the 73 and 53 kDa f orms. (C) 1999 Elsevier Science B.V. All rights reserved.