Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary purpose of this review is to address the progress towards small molecule modulators of human Transient Receptor Potential Canonical proteins (TRPC1, TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7). These proteins generate channels for calcium and sodium ion entry. They are relevant to many mammalian cell types including acinar gland cells, adipocytes, astrocytes, cardiac myocytes, cochlea hair cells, endothelial cells, epithelial cells, fibroblasts, hepatocytes, keratinocytes, leukocytes, mast cells, mesangial cells, neurones, osteoblasts, osteoclasts, platelets, podocytes, smooth muscle cells, skeletal muscle and tumour cells. There are broad-ranging positive roles of the channels in cell adhesion, migration, proliferation, survival and turning, vascular permeability, hypertrophy, wound-healing, hypo-adiponectinaemia, angiogenesis, neointimal hyperplasia, oedema, thrombosis, muscle endurance, lung hyper-responsiveness, glomerular filtration, gastrointestinal motility, pancreatitis, seizure, innate fear, motor coordination, saliva secretion, mast cell degranulation, cancer cell drug resistance, survival after myocardial infarction, efferocytosis, hypo-matrix metalloproteinase, vasoconstriction and vasodilatation. Known small molecule stimulators of the channels include hyperforin, genistein and rosiglitazone, but there is more progress with inhibitors, some of which have promising potency and selectivity. The inhibitors include 2-aminoethoxydiphenyl borate, 2-aminoquinolines, 2-aminothiazoles, fatty acids, isothiourea derivatives, naphthalene sulfonamides, N-phenylanthranilic acids, phenylethylimidazoles, piperazine/piperidine analogues, polyphenols, pyrazoles and steroids. A few of these agents are starting to be useful as tools for determining the physiological and pathophysiological functions of TRPC channels. We suggest that the pursuit of small molecule modulators for TRPC channels is important but that it requires substantial additional effort and investment before we can reap the rewards of highly potent and selective pharmacological modulators.
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PMID:In pursuit of small molecule chemistry for calcium-permeable non-selective TRPC channels -- mirage or pot of gold? 2376 62

Alligator gar Atractosteus spatula acclimated to brackish water (9 ppt) were exposed to water accommodated fraction oil loadings (surrogate to Macondo Deepwater Horizon, northern Gulf of Mexico) of 0.5 and 4.0 gm oil/L tank water for 48 h. The surrogate oil was approximately 98% alkanes and alkynes and 2% petroleum aromatic hydrocarbons. The 2% petroleum aromatic hydrocarbons were predominately naphthalene. After 48 h, naphthalene levels in fish liver exposed to 0.5 or 4 gm oil/L were 547.79 and 910.68 ppb, while muscle levels were 214.11 and 253.84 ppb. There was a significant decrease in peripheral blood lymphocyte numbers and a significant reduction of granulocytes in the kidney marrow of the same fish. Tissue changes included hepatocellular vacuolization and necrosis, necrotizing pancreatitis, renal eosinophilia, and splenic congestion. After 7 days recovery, liver naphthalene levels decreased to 43.59 and 43.20 ppb, while muscle levels decreased to 9.74, and 16.78 ppb for oil exposures of 0, 0.5 or 4 g/L. In peripheral blood and kidney marrow, blood cell counts returned to normal. The severity of liver and kidney lesions lessened after 7 days recovery in non-oiled water, but splenic congestion remained in all gar.
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PMID:Tissue PAH, blood cell and tissue changes following exposure to water accommodated fractions of crude oil in alligator gar, Atractosteus spatula. 2595 43