Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:129-03-3 (Cyproheptadine)
 258 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biosynthesis of proinsulin was measured by the incorporation of radiolabelled leucine and phenylalanine into carp islet protein. Even in the absence of glucose or amino acids in the medium the share of proinsulin in the total protein biosynthesis amounted to 40% of the total incorporated [3H]-leucine during 2 h of incubation. Glucose increased the rate of total protein biosynthesis in carp islets by approximately 20%, but no preferential increase of proinsulin synthesis occurred in the presence of glucose. Furthermore leucine did not increase [3H]-phenylalanine incorporation into proinsulin. Cyproheptadine, a specific inhibitor of proinsulin biosynthesis in mammals, did not inhibit in carp islets. The total protein synthesis was strongly dependent on the temperature. The share of proinsulin synthesis decreased from 40% at 17 degrees C to 20% at 4 degrees C. Even more drastically, the conversion of proinsulin to insulin became slower at lower temperatures and was undetectable at 4 degrees C. The results indicate that in contrast to mammals, in islets of the poikilotherm carp, metabolic substrates may play a less important role that the temperature in the regulation of insulin biosynthesis.
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PMID:Regulation of insulin biosynthesis in carp islets (Cyprinus carpio). 702 Mar 9

1. Metabolites formed during incubation of the antihistamine cyproheptadine hydrochloride with the zygomycete fungus Cunninghamella elegans in liquid culture were determined. The metabolites were isolated by hple and identified by mass spectrometric and proton nmr spectroscopic analysis. Two C elegans strains, ATCC 9245 and ATCC 36112, were screened and both produced essentially identical metabolites. 2. Within 72 h cyproheptadine was extensively biotransformed to at least eight oxidative phase-I metabolites primarily via aromatic hydroxylation metabolic pathways. Cyproheptadine was biotransformed predominantly to 2-hydroxycyproheptadine. Other metabolites identified were 1- and 3-hydroxycyproheptadine, cyproheptadine 10,11-epoxide, N-desmethylcyproheptadine, N-desmethyl-2-hydroxycyproheptadine, cyproheptadine N-oxide, and 2-hydroxycyproheptadine N-oxide. Although a minor fungal metabolite, cyproheptadine 10,11-epoxide represents the first stable epoxide isolated from the microbial biotransformation of drugs. 3. The enzymatic mechanism for the formation of the major fungal metabolite, 2-hydroxycyproheptadine, was investigated. The oxygen atom was derived from molecular oxygen as determined from 18O-labelling experiments. The formation of 2-hydroxycyproheptadine was inhibited 35, 70 and 97% by cytochrome P450 inhibitors metyrapone, proadifen and 1-aminobenzotriazole respectively. Cytochrome P450 was detected in the microsomal fractions of C. elegans. In addition, 2-hydroxylase activity was found in cell-free extracts of C. elegans. This activity was inhibited by proadifen and CO, and was inducible by naphthalene. These results are consistent with the fungal epoxidation and hydroxylation reactions being catalysed by cytochrome P450 monooxygenases. 4. The effects of types of media on the biotransformation of cyproheptadine were investigated. It appears that the glucose level significantly affects the biotransformation rates of cyproheptadine; however it did not change the relative ratios between metabolites produced.
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PMID:Fungal transformations of antihistamines: metabolism of cyproheptadine hydrochloride by Cunninghamella elegans. 914 Dec 37

In crustaceans, serotonin (5-HT) controls various physiological processes, such as hormonal secretion, color changes, reproduction, and metabolism. Since 5-HT injections cause hyperglycemia, this study was designed to further investigate this action of 5-HT in the crab Neohelice granulate, fed with a high-carbohydrate (HC) or a high-protein (HP) diet. The effects of pre-treatment with mammalian 5-HT receptor antagonists, cyproheptadine and methiothepin, were also investigated. A series of in vivo experiments with (3)H-5-HT was carried out in order to investigate the presence of putative receptors in peripheral tissues. Since gills were the tissue with the highest labeling in in vivo experiments, in vitro studies with isolated anterior and posterior gills were also conducted. Cyproheptadine blocked the hyperglycemic effect of 5-HT in HP-fed crabs. Methiothepin reduced glycogen levels in the anterior gills of HP crabs and partially blocked the 5-HT-like posture. The injection of (3)H-5-HT identified specific binding sites in all the tissues studied and revealed that the binding can be influenced by the type of diet administered to the crabs. Incubation of the anterior and posterior gills with (3)H-5-HT and 5-HT confirmed the specificity of the binding sites. Both antagonists inhibited (3)H-5-HT binding. In conclusion, this study highlights the importance of serotonin in the control of glucose homeostasis in crustaceans and provides evidences of at least two types of 5-HT binding sites in peripheral tissues. Further studies are necessary to identify the structure of these receptors and their signaling pathways.
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PMID:Serotonin effects in the crab Neohelice granulata: Possible involvement of two types of receptors in peripheral tissues. 2581 Mar 62


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