Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Involvement of ornithine decarboxylase (ODC) in proliferation of the HT29 cell line and its control by either fetal calf serum (FCS) or vasoactive intestinal peptide (VIP) as an external signal increasing cAMP level were investigated. Activation of the polyamine-producing system appears to be a necessary step in the proliferative response of HT29 cells since cell growth is arrested by addition of difluoromethylornithine (DFMO, an inhibitor of ODC), then restored by further addition of putrescine into the culture medium. FCS deprivation results in decreased activity of ODC and arrest of cell growth. Addition of FCS induces reactivation of ODC peaking at 9 hr and re-initiates proliferation but does not affect cAMP level. VIP strongly and rapidly stimulated cAMP accumulation, which resulted in significant activation of ODC. When VIP-induced cAMP formation was hindered by the alpha 2-adrenergic agonist UK14304, activation of ODC was no longer observed. The dose-response curve for ODC activation by VIP indicates an EC50 value of 0.078 nM which falls within the range of physiological concentrations for this peptide. However, VIP fails to stimulate proliferation when cells are cultured either in an FCS-free medium or in the presence of a growth-limiting concentration of FCS. We conclude that the mechanisms of ODC activation by either FCS or VIP are different, the latter involving cAMP formation. Activation of ODC to produce polyamines is necessary to support the proliferative process in our model but the VIP-induced activation of the enzyme alone is not sufficient to promote cell growth.
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PMID:Involvement of ornithine decarboxylase in the control of proliferation of the HT29 human colon cancer cell line. Effect of vasoactive intestinal peptide on enzyme activity. 184 59

In parotid, sublingual and submaxillary glands stimulated by continuous intravenous infusion of the neuropeptides substance P or vasoactive intestinal peptide at various doses for 3 h, the concentrations of the polyamines putrescine, spermidine, spermine and N1-acetylspermidine as well as the activity of ornithine decarboxylase were determined. This enzyme catalyses the synthesis of putrescine and is the key enzyme in polyamine formation. Vasoactive intestinal peptide induced the most marked effects, and the most conspicuous findings were made in the sublingual glands, where the ornithine decarboxylase activity was found to have increased more than 100-fold, accompanied by an increased level of putrescine in those glands which were removed immediately after the end of the infusion. When, instead, the glands were removed 5 h after the end of the infusion there was no longer any increase in the activity of ornithine decarboxylase or in putrescine concentration, but now spermidine and spermine were found to be increased. Interestingly, the parasympathetic non-adrenergic, non-cholinergic regulation of polyamine metabolism in the major salivary glands of the rat is most predominant in the sublingual glands.
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PMID:Substance P and vasoactive intestinal peptide influence polyamine metabolism in salivary glands of the rat. 247

The effects of combined administration of vasoactive intestinal peptide (VIP) and the ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on development of colon tumors induced by azoxymethane (AOM), on ODC activity of the colon wall, and on the labelling index of colon epithelial cells were investigated in inbred Wistar rats. Rats received weekly subcutaneous injections of AOM for 10 weeks and subcutaneous injections of VIP every other day and drinking water containing DAP (2.5 milligrams) ad libitum until the end of the experiment at week 45. Administration of VIP significantly increased the incidence of colon tumors at week 45. It also resulted in significant increases in colon ODC activity and in the labelling index during administration of AOM, but not after its cessation. Administration of both DAP and VIP significantly reduced the enhanced colon carcinogenesis by VIP. The DAP significantly attenuated the VIP enhancement of colon ODC activity and of the labelling index during AOM administration. These findings indicate that ODC inhibition attenuated enhancement of colon carcinogenesis, and suggest that enhancement of colon carcinogenesis by VIP may be mediated through its polyamine biosynthesis.
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PMID:Attenuation of vasoactive intestinal peptide enhancement of colon carcinogenesis by ornithine decarboxylase inhibitor. 762 32