Rat stomach ECL cells: mode of activation of histidine decarboxylase.
Histidine decarboxylase (HDC) occurs in ECL cells in the oxyntic mucosa of rat stomach. It is activated by gastrin. Refeeding of fasted rats or treatment with the proton pump inhibitor omeprazole promptly raised the serum gastrin concentration and consequently the HDC activity and the HDC protein content of the oxyntic mucosa. The food- and omeprazole-induced increase in HDC mRNA expression in the oxyntic mucosa was modest by comparison. Blockade of translation (cycloheximide) but not transcription (actinomycin D) prevented the postprandial rise in HDC activity. The half-life of HDC activity (after blockade of translation) was 94 min in omeprazole-treated rats and 55 min in fasted controls. The rate of enzyme synthesis was estimated to be 15 times higher in omeprazole-treated rats than in fasted controls. Inhibition of histamine uptake into ECL-cell granules by reserpine, a blocker of the vesicular monoamine transporter type-2, lowered the HDC activity and prevented the gastrin-induced HDC activation. We suggest that HDC activation reflects enhanced transcription, translation and/or posttranslational enzyme activation as well as stabilization, and that a high cytosolic histamine concentration suppresses HDC activation.
Zhao
C-M
CM
Department of Medical Technology, Faculty of Technology, Sør-Trøndelag University College, Trondheim, Norway. chun-mei.zhao@medisin.ntnu.no
Chen
D
D
Yamada
H
H
Dornonville de la Cour
C
C
Lindström
E
E
Persson
L
L
Håkanson
R
R
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D019861:Enterochromaffin-like Cells / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D005215:Fasting; D005502:Food; D005753:Gastric Mucosa / Q000166:cytology / Q000201:enzymology*; D005755:Gastrins / Q000097:blood / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D019518:Postprandial Period; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology
D005755:Gastrins; D012333:RNA, Messenger; D003609:Dactinomycin; D012110:Reserpine; D003513:Cycloheximide; D006640:Histidine Decarboxylase; D009853:Omeprazole