Drugs online research references
Gut. 1990 Feb;31(2):162-9.
Diarrhoea of famine and malnutrition--investigations using a rat model. 2--Ileal hypersecretion induced by starvation.
Young A, Levin RJ.
Department of Biology, Pharmaceutical Division, Reckitt & Colman, Kingston-upon-Hull.
The effects of progressive starvation for up to three days on the basal and secretagogue stimulated secretory functions of the rat ileum were investigated in vitro and in vivo. The secretagogues used included agents acting via cyclic AMP (dibutyryl cyclic AMP, theophylline, forskolin, and PGE2) and those acting via Ca++ (acetylcholine, bethanecol, carbachol, 5-hydroxytryptamine, and A23187). Starving rats for 24 h (day 1) had no effect on the basal electrogenic secretion (measured as the short circuit current, Isc muamps/cm2) or on the stimulated maximum electrogenic secretion (measured as the delta Isc where delta Isc = maxIsc-basal Isc). By day 2 of starvation, however, both the basal Isc and the delta Isc induced by all the secretagogues were significantly greater than in the fed and increased even more on day 3. Replacement of all the chloride ions and inhibition by furosemide indicated that the enhanced secretion was due mainly to chloride ions. Cholinergic stimulation was blocked by atropine, indicating the stimulation was via muscarinic receptors while cholinergic dose - delta Isc response curves for fed and starved ilea showed significantly increased maximum electrogenic secretory response in the latter but no evidence of any change in the affinity (ED50) of the receptors mediating the response. The basal secretion and the secretory response to acetylcholine in both fed and starved ilea was unaffected by tetrodotoxin, revealing that the enhanced secretory response could be expressed via the muscarinic receptors on the enterocytes without the enteric neural network. Measurement of ileal fluid movement in vivo showed that in fed and day 1 starved rats the basal, unstimulated 'tone' of the ileum was absorptive. On day 2, however, the basal 'tone' had reversed to one of secretion which increased further on day 3. Stimulation of fluid secretion in vivo by bethanecol, carbachol, or PGE2 induced larger increases in the starved ilea by day 2 which increased even further on day 3. Lumenal chloride and bicarbonate concentrations were greater in the starved ileal fluid than in the fed. The studies in rat ileum confirm and extend those on rat jejunum and indicate that starvation creates a hypersensitive small bowel that responds to secretagogues and cholinergic neurotransmitters with a greatly enhanced secretory response.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2311974&dopt=Abstract
Drug Metab Dispos. 1992 Nov-Dec;20(6):882-8.
Microbial models of mammalian metabolism. N-dealkylation of furosemide to yield the mammalian metabolite CSA using Cunninghamella elegans.
Hezari M, Davis PJ.
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Texas, Austin 78712-1074.
Furosemide (Lasix), a widely used diuretic, is metabolized by the fungus Cunninghamella elegans (ATCC 36112) to 4-chloro-5-sulfamoyl anthranilic acid (CSA), a metabolite also present in mammalian systems. This metabolite was isolated following preparative-scale incubations of C. elegans, and was characterized by comparison with standard CSA using 13C-NMR, mass spectrometry (high-resolution mass spectra, electron impact mass spectra), UV, TLC, and HPLC with fluorescence detection. Because a known complication with furosemide studies is the spontaneous formation of CSA by decomposition of furosemide during incubation, extraction, and/or analysis, a time course study was conducted to determine the rate of CSA formation caused by metabolism vs. the relatively low rate of CSA formation caused by spontaneous decomposition.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1362941&dopt=Abstract
Drug Metab Dispos. 1993 Mar-Apr;21(2):259-67.
Microbial models of mammalian metabolism. Furosemide glucoside formation using the fungus Cunninghamella elegans.
Hezari M, Davis PJ.
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Texas, Austin 78712-1074.
The diuretic furosemide (Lasix) was metabolized by the fungus Cunninghamella elegans (ATCC 36112) to the phase II conjugate, furosemide acyl glucoside. This metabolite was isolated following semipreparative scale incubations of C. elegans involving glucose nutrient dosing, and was characterized by NMR spectroscopy (1H and 1H/1H correlated), MS (FAB), UV, HPLC with fluorescence detection, and enzymatic treatments. The aglycone fragment of the conjugate was characterized as furosemide by treatment of the metabolite with sodium hydroxide, whereas the sugar part was identified as glucose by cleavage of the conjugate, derivatization of the released sugar, and GC/MS analysis.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8097695&dopt=Abstract
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