Effect of gastrin receptor blockade on gastrin and histidine decarboxylase gene expression in rats during achlorhydria.
BACKGROUND
Gastrin stimulates histidine decarboxylase (HDC) activity and proliferation of enterochromaffin-like (ECL) cells. Furthermore, it has been suggested that gastrin controls HDC gene expression. We therefore analysed the effect of gastrin receptor blockade by PD 136 450 (CAM 1189) on HDC gene expression. The influence of PD 136 450 on gastrin, somatostatin, and chromogranin A was also evaluated.


METHODS
Gene expression of HDC, gastrin, somatostatin, and chromogranin A (CgA) was analysed by Northern blot analyses after 14 days' application of the proton pump inhibitor BY 308 and/or the gastrin/cholecystokinin B receptor antagonist PD 136 450.


RESULTS
PD 136 450 had no significant effect on gastrin mRNA or somatostatin mRNA in controls and during proton pump inhibition. BY 308 treatment resulted in a marked induction of HDC and CgA mRNA, whereas concomitant PD 136 450 in a concentration previously shown to suppress maximal pentagastrin-induced gastric acid secretion and to prevent BY 308-induced ECL cell proliferation did not result in significant alteration. PD 136 450 increased HDC significantly and CgA mRNA to a lesser extent in normogastrinaemic rats, whereas previous work showed a decreased ECL cell labelling index.


CONCLUSIONS
These data suggest that there are independent regulatory pathways for ECL cell proliferation and gene expression. Other factors besides gastrin may act through PD 136 450-insensitive pathways to control HDC and CgA gene expression.
Simon
B
B
Dept. of Internal Medicine, Philipps University, Marburg, Germany.
Eissele
R
R
Czornik
M
M
Swarovsky
B
B
Arnold
R
R
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000126:Achlorhydria / Q000139:chemically induced / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D053379:Chromogranin A; D002864:Chromogranins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005755:Gastrins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D006640:Histidine Decarboxylase / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D007211:Indoles / Q000494:pharmacology*; D009853:Omeprazole / Q000031:analogs & derivatives / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013004:Somatostatin / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D053379:Chromogranin A; D002864:Chromogranins; D004791:Enzyme Inhibitors; D005755:Gastrins; D007211:Indoles; D010627:Phenethylamines; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; C077645:PD 136450; D013004:Somatostatin; C049708:B 823-08; D006640:Histidine Decarboxylase; D009853:Omeprazole