Secretory activity in isolated rat stomach ECL cells
Research output: Thesis › Doctoral Thesis (compilation)
ECL cells are endocrine/paracrine cells located in the acid-producing part of the stomach. They are important regulators of gastric acid secretion in the stomach by virtue of their histamine synthesizing and secreting capacity. Histamine in turn stimulates parietal cells to secrete acid. The ECL cell also contains the endocrine polypeptide chromogranin A (CGA) and CGA-derived peptides such as pancreastatin. The aim of the study was to identify regulators of secretory activity in isolated and purified ECL cells and to elucidate their signal transduction pathways. The effect of histamine reduction by various mechanisms was studied along with screening of a wide-range of CCK2 receptor antagonists. Gastrin and PACAP stimulated both histamine and pancreastatin secretion from isolated ECL cells. VIP, PHI and adrenaline also evoked secretion but to a lesser extent. Muscarinic agonists failed to induce secretion. Gastrin and PACAP-evoked secretion depended upon Ca2+-influx through multiple Ca2+-channels in the cell membrane. Somatostatin, galanin and PGE2 were effective inhibitors of ECL-cell secretion. Histamine did not exert any autoinhibitory effects. The ECL cells synthesized PGE2 in response to inflammatory mediators such as IL-1B, TNF-a and bradykinin. Histamine depletion was evoked by interfering with histamine production using a-FMH or by interfering with intracellular transport using reserpine or bafilomycin A1. Neither pancreastatin storage nor secretion were affected by histamine depletion. The CCK2 receptor antagonists YM022, YF476 and AG041R were the most potent antagonists tested at inhibiting gastrin-evoked secretion. pKB values ranged between 10.4 – 11.3. YM022 and YF 476 acted in a competitive manner.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Award date||2000 May 5|
|Publication status||Published - 2000|
Defence details Date: 2000-05-05 Time: 10:15 Place: Lecture Hall, Dept. of Pharmacology External reviewer(s) Name: Prinz, Christian Title: Dr Affiliation: [unknown] ---