Effect of the histamine (H2) inhibitor metiamide on histamine-stimulated bile flow in dogs

1976 ◽  
Vol 231 (2) ◽  
pp. 516-521 ◽  
Author(s):  
DL Kaminski ◽  
MJ Ruwart ◽  
M Jellinek
Keyword(s):  
Bile Flow ◽  
Competitive Inhibition ◽  
Acid Output ◽  
Hydrogen Ion ◽  
Receptor Interaction ◽  
Maximal Response ◽  
H2 Receptor Antagonist ◽  
Hepatic Bile ◽  
Histamine H2 Receptor ◽  
H2 Receptor

The effects of the histamine H2-receptor inhibitor metiamide on histamine-stimulated canine bile flow and gastric hydrogen ion output were evaluated. Histamine was found to stimulate bile volume in doses comparable to those that stimulated gastric hydrogen ion output; both responses appeared to have the same maximal response dose, 150 mug/kg per h. Metiamide alone did not alter hepatic bile flow. Administration of metiamide, 2 mg/kg per h, along with various doses of histamine demonstrated that the H2-receptor antagonist decreased bile volume and gastric hydrogen ion output from values obtained with histamine administration alone. The D50 of histamine for bile flow was 16.3 mug/kg per h and the D50 for hydrogen ion output was 44.2 mug/kg per h, Kinetic analysis suggests that the decrease in histamine-stimulated hydrogen ion output produced by metiamide is the result of competitive inhibition; the decrease in histamine-stimulated bile volume by metiamide which is different from the hydrogen ion inhibition, suggests noncompetitive inhibition. These data indicate that the mechanism of histamine choleresis is different from the mechanism of histamine-stimulated gastric acid output and that histamine-stimulated bile flow may not be the result of direct hormone-receptor interaction.

Up- and down-regulation of membrane receptors as possible mechanisms related to the antiulcer actions of milk in rat gastric mucosa

1987 ◽  
Vol 7 (2) ◽  
pp. 135-142 ◽  
Author(s):  
C. Gespach ◽  
S. Emami ◽  
E. Chastre ◽  
J.-M. Launay ◽  
G. Rosselin
Keyword(s):  
Gastric Mucosa ◽  
Competitive Inhibition ◽  
Membrane Receptors ◽  
Receptor Activity ◽  
Milk Diet ◽  
H2 Receptor Antagonist ◽  
Adult Rats ◽  
Parallel Displacement ◽  
Histamine H2 Receptor ◽  
H2 Receptor

The effects of a cow's milk diet on receptor activity and histamine metabolism in gastric glands and mucosa isolated from adult rats were examined. The milk diet was associated with (1) a decreased mobilization of H2 receptors by histamine and (2) an increased mobilization of PGE2 (prostaglandin E2) receptors in mucous cells (cytoprotective effect) and parietal cells (antiacid effect). These changes are not observed for the receptors reducing pentagastrin- and histamine-induced gastric acid secretion (pancreatic/enteroglucagons, somatostatin) and stimulating mucus, bicarbonate and pepsin secretions in the rat (secretin). Cimetidine produced a parallel displacement of the histamine dose-response curve, suggesting competitive inhibition between this classical H2 receptor antagonist and histamine in the two experimental groups. Prostaglandins and other components in milk such as EGF (epidermal growth factor) and somatostatin might therefore protect gastric mucosa by a differential control of PGE2 and histamine H2 receptor activity either directly (PGE2 in milk) or indirectly (inhibition of endogeneous histamine synthesis/release and stimulation of PGE-I synthesis/release).

The metabolism in animals and man of oxmetidine—A new histamine H2-receptor antagonist

Xenobiotica ◽  
1984 ◽  
Vol 14 (7) ◽  
pp. 509-514 ◽  
Author(s):  
P. J. Cox ◽  
W. M. H. Heijbroek ◽  
D. C. Taylor ◽  
P. J. Wood ◽  
P. R. Cresswell ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
H2 Receptor Antagonist ◽  
Histamine H2 Receptor ◽  
H2 Receptor ◽  
Histamine H2 Receptor Antagonist

scholarly journals An Antibody From a Patient With Ranitidine-Induced Thrombocytopenia Recognizes a Site on Glycoprotein IX That Is a Favored Target for Drug-Induced Antibodies

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2359-2365 ◽  
Author(s):  
G. Gentilini ◽  
B.R. Curtis ◽  
R.H. Aster
Keyword(s):  
Tight Binding ◽  
Chinese Hamster ◽  
Severe Thrombocytopenia ◽  
H2 Receptor Antagonist ◽  
Drug Induced ◽  
Histamine H2 Receptor ◽  
H2 Receptor ◽  
Drug Dependent ◽  
A Site ◽  
Common Target

Although thrombocytopenia associated with the use of histamine H2 receptor (H2R) antagonists has been described, a drug-dependent, platelet-reactive antibody has not previously been identified in such cases. We studied serum from a patient who developed acute, severe thrombocytopenia after exposure to the H2 receptor antagonist, ranitidine, and identified an antibody that reacted with normal platelets in the presence of this drug at pharmacologic concentrations. In flow cytometric and immunoprecipitation studies, the antibody was shown to be specific for the glycoprotein Ib/IX complex (GPIb/IX). From the pattern of monoclonal antibody (MoAb) inhibition and the reactions of antibody with Chinese hamster ovary (CHO) cells transfected with GPIX and GPIbβ, we found that the patient's antibody is specific for an epitope on GPIX close to, or identical with a site recognized by the MoAb SZ1 that is a common target for antibodies induced by quinine and quinidine, drugs structurally unrelated to ranitidine. These findings provide evidence that immune thrombocytopenia can be caused by sensitivity to an H2 R antagonist and suggest that the SZ1 binding site on GPIX may be a common target for drug-induced antibodies. Further studies of the epitope for which SZ1 is specific may provide clues to the mechanism(s) by which drugs promote tight binding of antibody to a membrane glycoprotein and cause platelet destruction in patients with drug sensitivity.

Sign in / Sign up

Export Citation Format

Share Document