Drugs online research references
Regul Pept. 1989 May;25(2):235-46.
Omeprazole and ranitidine, antisecretagogues with different modes of action, are equally effective in causing hyperplasia of enterochromaffin-like cells in rat stomach.
Ryberg B, Bishop AE, Bloom SR, Carlsson E, Hakanson R, Larsson H, Mattsson H, Polak JM, Sundler F.
AB Hassle, Dept. of Biolopgy, Molndal, Sweden.
Female rats were treated for 28 days with high doses of the gastric acid secretion inhibitors omeprazole and ranitidine. Omeprazole, which is long-acting, was given orally once daily. Ranitidine, which is short-acting, was given by continuous infusion (via osmotic minipumps, implanted subcutaneously). The aim was to produce a similar degree of acid inhibition with the two drugs. The inhibition of acid secretion over the day and night was more pronounced in the omeprazole-treated rats (maximal inhibition 100%, minimum 85%) than in those receiving ranitidine (mean 70%). In both groups, there was a great increase in plasma gastrin, somewhat greater after omeprazole than after ranitidine. The gastrin concentration in the antrum was almost doubled by both treatments and there was a moderate increase in the number of antral gastrin cells in the omeprazole-treated rats. The number of enterochromaffin-like (ECL) cells (per visual field) increased in the oxyntic mucosa to the same extent (greater than 100%) in the ranitidine- and omeprazole-treated rats. Apart from the gastrin cells in the antrum and the ECL cells in the corpus no other gastric endocrine cell type seemed to respond to treatments with antisecretagogues. We conclude that, regardless of the type of antisecretagogue used, effective and long-term suppression of gastric acid secretion results in sustained hypergastrinemia and increased number of ECL cells. Conceivably therefore, the ECL cell hyperplasia reflects the trophic effect of gastrin.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2756157&dopt=Abstract
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Biochim Biophys Acta. 1993 Feb 23;1146(1):73-80.
The site of acid secretion in the mammalian parietal cell.
Scott DR, Helander HF, Hersey SJ, Sachs G.
Department of Physiology and Medicine, UCLA.
Initiation of acid secretion in the gastric mucosa is accompanied by a morphological transformation in which the acid pump, the H+/K(+)-ATPase, translocates from a cytoplasmic vesicular location to the secretory surface lining the canaliculi. Associated with the morphological changes, activation of K+ and Cl- pathways are necessary to supply K+ to the extracytoplasmic face of the pump. Although the pump in the secretory membrane is known to secrete acid, it is not known whether activation of the KCl pathway occurs in the tubulovesicular membrane prior to the formation of the canaliculus, or when the pump is in the secretory membrane. The cellular site of activation of acid secretion in the rabbit gastric parietal cell was investigated using the covalent binding of [3H]omeprazole as a probe of acid secretion in rabbit gastric glands that were undergoing stimulation in vitro. This compound depends on an acidic environment for activation and covalent binding to the H+/K(+)-ATPase. Electron microscopic autoradiography showed that activation of the enzyme occurred only when it was present in the canalicular membrane and not when it was present in the cytoplasmic tubulovesicular membrane. Hence there is likely to be a physical separation of K+ and/or Cl- pathways from the ATPase in the resting cell, and stimulation of acid secretion is dependent on colocalization of these pathways in the canalicular membrane.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8382956&dopt=Abstract
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ims.u-tokyo.ac.jp
Induction of DNA single-strand scission by four glandular stomach carcinogens and three other chemicals was studied in the pyloric mucosa of rat stomach after gastric intubation. DNA single-strand scission, as was measured by the alkaline elution method, was induced by four glandular stomach carcinogens; N-nitroso N-methylurethane at doses of 1 and 9 mg/kg body wt, 4-nitroquinoline 1-oxide at 20 and 30 mg/kg body wt. N-ethyl-N'-nitro-N-nitrosoguanidine at 30 and 100 mg/kg body wt and N-propyl-N'-nitro-N-nitrosoguanidine at 30 and 100 mg/kg body wt. DNA single-strand scission was also induced dose-dependently by a direct acting mutagen, 1-nitrosoindole-3-acetonitrile at doses of 100, 500 and 800 mg/kg body wt. Omeprazole, a proton pump inhibitor, was equivocal in its effect in this assay at 30-500 mg/kg body wt: induction was statistically significant by Cochran-Armitage binomial trend test. Loxtidine, an H2-receptor antagonist, did not induce DNA single-strand breaks in the pyloric mucosa at a dose of 400 mg/kg body wt. The present results together with previous information suggest that DNA single-strand scission is a good marker for tumor-initiating activity in rat stomach mucosa.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8637505&dopt=Abstract
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