Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secretion rates of >700 individual glands in isolated tracheal mucosa from 56 adult pigs were monitored optically. "Basal" secretion of 0.7 +/- 0.1 nl x min(-1) gland(-1) was observed 1-9 h post-harvest but was near zero on day 2. Secretion to carbachol (10 microm) peaked at 2-3 min and then declined to a sustained phase. Peak secretion was 12.4 +/- 1.1 nl x min(-1) gland(-1); sustained secretion was approximately one-third of peak secretion. Thapsigargin (1 microm) increased secretion from 0.1 +/- 0.05 to 0.7 +/- 0.2 nl x min(-1) gland(-1); thapsigargin did not cause contraction of the trachealis muscles. Isoproterenol and phenylephrine (10 microm each) were ineffective, but vasoactive intestinal peptide (1 microm) and forskolin (10 microm) each produced sustained secretion of 1.0 +/- 0.5 and 1.7 +/- 0.2 nl x min(-1) gland(-1), respectively. The density of actively secreting glands was 1.3/mm(2). Secretion to either carbachol or forskolin was inhibited (approximately 50%) by either bumetanide or HCO(3)(-) removal and inhibited approximately 90% by the combined treatments. Mucus secreted in response to carbachol or forskolin was acidic by approximately 0.2 pH units relative to the bath and remained acidic by approximately 0.1 pH units after bumetanide. The strong secretory response to vasoactive intestinal peptide, the acidity of [cAMP](i)-stimulated mucus, and its inhibition by bumetanide were unexpected.
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PMID:Mucus secretion from single submucosal glands of pig. Stimulation by carbachol and vasoactive intestinal peptide. 1201 Oct 87

The human ileocaecal adenocarcinoma cell line HCT-8 was characterized for its potential as an in vitro organ-specific model for gastro-intestinal toxicity. HCT-8 cells showed typical epithelial cell morphology, with microvilli and intercellular junctional complexes, and formed domes, consistent with transepithelial fluid secretion. The cells express three intestinal brush-border enzyme activities (alkaline phosphatase, leucine aminopeptidase and alpha-glucosidase), and adenylate cyclase can be stimulated with vasoactive intestinal peptide. The toxicity of eight non-steroidal anti-inflammatory drugs (NSAID; indomethacin, mefenamic acid, ketoprofen, ibuprofen, sulindac, aspirin, phenylbutazone and naproxen) were assessed using the MTT and neutral red uptake assays. The MTT assay was consistently a more sensitive measure of NSAID-induced toxicity, which suggests that perturbation of mitochondrial function may be an early event in NSAID-induced cellular damage. Comparing the rankings observed in acute studies in the rat in vivo with those observed with HCT-8 cells, there are some general agreements. Indomethacin, a potent ulcerogen in vivo, was consistently among the most toxic in vitro, while aspirin and phenylbutazone have comparatively low rankings in vitro and in vivo. In man, with chronic administration, indomethacin is again ranked as a potent ulcerogen, as is aspirin, in contrast to the in vitro data with HCT-8. Therefore, NSAID-induced toxicity in HCT-8 cells assessed by the MTT or neutral red assays, can only partially predict toxicity in vivo, which suggests that local gastro-intestinal environmental factors, such as luminal acidity, may play a role in vivo. The ability of HCT-8 cells to reconstitute intact epithelial layers, thereby allowing such environmental factors to be mimicked, allows further development of these cells as a model for the in vitro prediction of in vivo gastro-intestinal toxicity.
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PMID:Toxic effects of non-steroidal anti-inflammatory drugs in a human intestinal epithelial cell line (HCT-8), as assessed by the MTT and neutral red assays. 2073 14