Effect of Cholecystokinin-B/Gastrin Receptor Antagonists on Rat Stomach ECL Cells

Research output: ThesisDoctoral Thesis (compilation)

Standard

Effect of Cholecystokinin-B/Gastrin Receptor Antagonists on Rat Stomach ECL Cells. / Ding, Xi-Qin.

Department of Pharmacology, Lund University, 1997. 156 p.

Research output: ThesisDoctoral Thesis (compilation)

Harvard

Ding, X-Q 1997, 'Effect of Cholecystokinin-B/Gastrin Receptor Antagonists on Rat Stomach ECL Cells', Doctor, Division of Clinical Chemistry and Pharmacology.

APA

Ding, X-Q. (1997). Effect of Cholecystokinin-B/Gastrin Receptor Antagonists on Rat Stomach ECL Cells. Department of Pharmacology, Lund University.

CBE

Ding X-Q. 1997. Effect of Cholecystokinin-B/Gastrin Receptor Antagonists on Rat Stomach ECL Cells. Department of Pharmacology, Lund University. 156 p.

MLA

Ding, Xi-Qin Effect of Cholecystokinin-B/Gastrin Receptor Antagonists on Rat Stomach ECL Cells Department of Pharmacology, Lund University. 1997.

Vancouver

Ding X-Q. Effect of Cholecystokinin-B/Gastrin Receptor Antagonists on Rat Stomach ECL Cells. Department of Pharmacology, Lund University, 1997. 156 p.

Author

Ding, Xi-Qin. / Effect of Cholecystokinin-B/Gastrin Receptor Antagonists on Rat Stomach ECL Cells. Department of Pharmacology, Lund University, 1997. 156 p.

RIS

TY - THES

T1 - Effect of Cholecystokinin-B/Gastrin Receptor Antagonists on Rat Stomach ECL Cells

AU - Ding, Xi-Qin

N1 - Defence details Date: 1997-05-27 Time: 10:15 Place: Department of Pharmacology External reviewer(s) Name: Schmidt, Wolfgang E Title: Professor Affiliation: Kiel, Germany ---

PY - 1997

Y1 - 1997

N2 - The histamine- and pancreastatin- containing ECL cells in the acid-producing mucosa of the rat stomach operate under the control of circulating gastrin. The present work examines how cholecystokinin (CCK)-B/gastrin receptors regulate the activity of the ECL cells. The oxyntic mucosal histidine decarboxylase (HDC) activity and the circulating pancreastatin concentration are two markers for the activity of the ECL cells. A series of candidate CCK-B/gastrin receptor antagonists was screened for their potency and selectivity in vivo with particular emphasis on their effect on the gastrin-evoked ECL-cell HDC activation. YF476, YM022, RP73870, JB93182 and AG041R were found to be potent and selective antagonists of the ECL-cell CCK-B/gastrin receptors, while the dipeptoid compounds PD136450, PD135158 and PD134308 were found to be partial agonists rather than antagonists. YM022 and RP73870 were selected for further studies. Sustained CCK-B/gastrin receptor blockade (7 days) impaired the functional activity of the ECL cells and prevented the adaptation of the ECL cells to hypergastrinemia as manifested in the reduced oxyntic mucosal HDC activity, histamine concentration and HDC mRNA and chromogranin A (CGA) mRNA concentrations and in the reduced serum pancreastatin concentration and the hypergastrinemia. CCK-B/gastrin receptor blockade deactivated the ECL cells according to a complex time pattern in which histamine and pancreastatin secretion and protein synthesis were promptly inhibited (hours to days) while longer times (days to weeks) were required to lower their histamine and pancreastatin contents. In addition, YM022 and RP73870 abolished the gastrin-induced gastric acid secretion without affecting the basal and vagally stimulated acid secretion. The results support the view that CCK-B/gastrin receptors are essential for the maintenance and adaptation of the ECL cells and for gastrin-stimulated gastric acid secretion.

AB - The histamine- and pancreastatin- containing ECL cells in the acid-producing mucosa of the rat stomach operate under the control of circulating gastrin. The present work examines how cholecystokinin (CCK)-B/gastrin receptors regulate the activity of the ECL cells. The oxyntic mucosal histidine decarboxylase (HDC) activity and the circulating pancreastatin concentration are two markers for the activity of the ECL cells. A series of candidate CCK-B/gastrin receptor antagonists was screened for their potency and selectivity in vivo with particular emphasis on their effect on the gastrin-evoked ECL-cell HDC activation. YF476, YM022, RP73870, JB93182 and AG041R were found to be potent and selective antagonists of the ECL-cell CCK-B/gastrin receptors, while the dipeptoid compounds PD136450, PD135158 and PD134308 were found to be partial agonists rather than antagonists. YM022 and RP73870 were selected for further studies. Sustained CCK-B/gastrin receptor blockade (7 days) impaired the functional activity of the ECL cells and prevented the adaptation of the ECL cells to hypergastrinemia as manifested in the reduced oxyntic mucosal HDC activity, histamine concentration and HDC mRNA and chromogranin A (CGA) mRNA concentrations and in the reduced serum pancreastatin concentration and the hypergastrinemia. CCK-B/gastrin receptor blockade deactivated the ECL cells according to a complex time pattern in which histamine and pancreastatin secretion and protein synthesis were promptly inhibited (hours to days) while longer times (days to weeks) were required to lower their histamine and pancreastatin contents. In addition, YM022 and RP73870 abolished the gastrin-induced gastric acid secretion without affecting the basal and vagally stimulated acid secretion. The results support the view that CCK-B/gastrin receptors are essential for the maintenance and adaptation of the ECL cells and for gastrin-stimulated gastric acid secretion.

KW - pharmacognosy

KW - Pharmacological sciences

KW - vävnadskultur

KW - histokemi

KW - cytokemi

KW - Histologi

KW - tissue culture

KW - histochemistry

KW - gastrin

KW - cholecystokinin (CCK) receptors

KW - ECL cells

KW - CCK-B/gastrin receptor antagonists

KW - histidine decarboxylase (HDC)

KW - histamine

KW - pancreastatin

KW - chromogranin A (CGA)

KW - gastric acid secretion.

KW - cytochemistry

KW - Histology

KW - pharmacy

KW - toxicology

KW - Farmakologi

KW - farmakognosi

KW - farmaci

KW - toxikologi

M3 - Doctoral Thesis (compilation)

SN - 91-628-2498-8

PB - Department of Pharmacology, Lund University

ER -