yf-476 and pancreastatin

yf-476 has been researched along with pancreastatin* in 3 studies

Reviews

1 review(s) available for yf-476 and pancreastatin

ArticleYear
CCK2 receptor antagonists: pharmacological tools to study the gastrin-ECL cell-parietal cell axis.
    Regulatory peptides, 1999, Mar-17, Volume: 80, Issue:1-2

    Gastrin-recognizing CCK2 receptors are expressed in parietal cells and in so-called ECL cells in the acid-producing part of the stomach. ECL cells are endocrine/paracrine cells that produce and store histamine and chromogranin A (CGA)-derived peptides, such as pancreastatin. The ECL cells are the principal cellular transducer of the gastrin-acid signal. Activation of the CCK2 receptor results in mobilization of histamine (and pancreastatin) from the ECL cells with consequent activation of the parietal cell histamine H2 receptor. Thus, release of ECL-cell histamine is a key event in the process of gastrin-stimulated acid secretion. The oxyntic mucosal histidine decarboxylase (HDC) activity and the serum pancreastatin concentration are useful markers for the activity of the gastrin-ECL cell axis. Powerful and selective CCK2 receptor antagonits have been developed from a series of benzodiazepine compounds. These agents are useful tools to study how gastrin controls the ECL cells. Conversely, the close control of ECL cells by gastrin makes the gastrin-ECL cell axis well suited for evaluating the antagonistic potential of CCK2 receptor antagonists with the ECL-cell HDC activity as a notably sensitive and reliable parameter. The CCK2 receptor antagonists YF476, YM022, RP73870, JB93182 and AG041R were found to cause prompt inhibition of ECL-cell histamine and pancreastatin secretion and synthesis. The circulating pancreastatin concentration is raised, was lowered when the action of gastrin on the ECL cells was blocked by the CCK2 receptor antagonists. These effects were associated with inhibition of gastrin-stimulated acid secretion. In addition, sustained receptor blockade was manifested in permanently decreased oxyntic mucosal HDC activity, histamine concentration and HDC mRNA and CGA mRNA concentrations. CCK2 receptor blockade also induced hypergastrinemia, which probably reflects the impaired gastric acid secretion (no acid feedback inhibition of gastrin release). Upon withdrawal of the CCK2 receptor antagonists, their effects on the ECL cells were readily reversible. In conclusion, gastrin mobilizes histamine from the ECL cells, thereby provoking the parietal cells to secrete acid. While CCK2 receptor blockade prevents gastrin from evoking acid secretion, it is without effect on basal and vagally stimulated acid secretion. We conclude that specific and potent CCK2 receptor antagonists represent powerful tools to explore the functional significance of the EC

    Topics: Animals; Benzodiazepines; Benzodiazepinones; Chromogranin A; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Histidine Decarboxylase; Hormone Antagonists; Humans; Indoles; Pancreatic Hormones; Parietal Cells, Gastric; Phenylurea Compounds; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Stomach

1999

Other Studies

2 other study(ies) available for yf-476 and pancreastatin

ArticleYear
Effect of cholecystokinin-2 receptor blockade on rat stomach ECL cells. A histochemical, electron-microscopic and chemical study.
    Cell and tissue research, 2000, Volume: 299, Issue:1

    The ECL cells in the oxyntic mucosa of rat stomach produce histamine and chromogranin A-derived peptides such as pancreastatin. The cells respond to gastrin via cholecystokinin-2 (CCK2) receptors. A CCK2 receptor blockade was induced by treatment (for up to 8 weeks) with two receptor antagonists, YM022 and YF476. Changes in ECL-cell morphology were examined by immunocytochemistry and electron microscopy, while changes in ECL cell-related biochemical parameters were monitored by measuring serum pancreastatin and oxyntic mucosal pancreastatin, and histamine concentrations, and histidine decarboxylase (HDC) activity. The CCK2 receptor blockade reduced the ECL-cell density only marginally, if at all, but transformed the ECL cells from slender, elongated cells with prominent projections to small, spherical cells without projections. The Golgi complex and the rough endoplasmic reticulum were diminished. Secretory vesicles were greatly reduced in volume density in the trans Golgi area. Circulating pancreastatin concentration and oxyntic mucosal HDC activity were lowered within a few hours. Oxyntic mucosal histamine and pancreastatin concentrations were reduced only gradually. The CCK2 receptor blockade was found to prevent the effects of omeprazole-evoked hypergastrinaemia on the ECL-cell activity and density. In conclusion, gastrin, acting on CCK2 receptors, is needed to maintain the shape, size and activity of the ECL cells, but not for maintaining the ECL-cell population.

    Topics: Animals; Benzodiazepines; Benzodiazepinones; Chromogranin A; Cytoplasmic Granules; Gastrins; Histamine; Histidine Decarboxylase; Hormone Antagonists; Immunohistochemistry; Male; Microscopy, Electron; Omeprazole; Pancreatic Hormones; Parietal Cells, Gastric; Phenylurea Compounds; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Time Factors

2000
Evaluation of three novel cholecystokinin-B/gastrin receptor antagonists: a study of their effects on rat stomach enterochromaffin-like cell activity.
    Pharmacology & toxicology, 1997, Volume: 81, Issue:5

    Gastrin stimulates rat stomach enterochromaffin-like (ECL) cells via activation of cholecystokinin-B/gastrin receptors. The stimulation is manifested in the activation of the histamine-forming enzyme histidine decarboxylase and in the secretion of histamine and pancreastatin, a chromogranin A-derived peptide. We have examined the short-term effects of three novel cholecystokinin-B/gastrin receptor antagonists (YF476, JB93182 and AG041R) on the ECL cells in intact fasted rats. The drugs and/or gastrin were infused intravenously for 3 hr and the oxyntic mucosal histidine decarboxylase activity and the serum pancreastatin concentration were measured. We also studied the effects of the three drugs on gastric emptying in mice, a cholecystokinin-A receptor-mediated response. YF476, JB93182 and AG041R antagonized the gastrin-evoked histidine decarboxylase activation in a dose-dependent manner. YF476, JB93182 and AG041R induced maximal inhibition at 0.03, 0.1 and 0.1 mumol kg-1 hr-1, respectively; the corresponding ID50 values were 0.002, 0.008, and 0.01 mumol kg-1 hr-1. YF476 was selected for further analysis. It produced a rightward shift of the gastrin dose-response curve, consistent with competitive inhibition. Moreover, it antagonized the omeprazole-evoked histidine decarboxylase activation and the gastrin- and omeprazole-induced rise in the circulating pancreastatin concentration. None of the three drugs tested inhibited gastric emptying or prevented the cholecystokinin-8s-induced inhibition of gastric emptying at the doses tested. The results show that YF476, JB93182 and AG041R are potent and selective cholecystokinin-B/ gastrin receptor antagonists, and that YF476 is 4-5 times more potent than JB93182 and AG041R.

    Topics: Animals; Benzodiazepinones; Chromogranin A; Enterochromaffin-like Cells; Enzyme Activation; Gastric Emptying; Gastrins; Histidine Decarboxylase; Hormone Antagonists; Indoles; Male; Omeprazole; Pancreatic Hormones; Phenylurea Compounds; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin

1997