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, i t has been suggested that gastrin controls HDC gene expression. We the refore analysed the effect of gastrin receptor blockade by PD 136 450 (CAM 1189) an HDC gene expression. The influence of PD 136 450 on gast rin, somatostatin, and chromogranin A was also evaluated. Methods: Gen e expression of HDC, gastrin, somatostatin, and chromogranin A (CgA) w as analysed by Northern blot analyses after 14 days' application of th e proton pump inhibitor BY 308 and/or the gastrin/cholecystokinin B re ceptor antagonist PD 136 450. Results: PD 136 450 had no significant e ffect on gastrin mRNA or somatostatin mRNA in controls and during prot on pump inhibition. BY 308 treatment resulted in a marked induction of HDC and CgA mRNA, whereas concomitant PD 136 450 in a concentration p reviously 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 significan tly and CgA mRNA to a lesser extent in normogastrinaemic rats, whereas previous work showed a decreased ECL cell labelling index. Conclusion s: These data suggest that there are independent regulatory pathways f or ECL cell proliferation and gene expression. Other factors besides g astrin may act through PD 136 450-insensitive pathways to control HDC and CgA gene expression.