Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sensitivity to phenylephrine, isoproterenol, serotonin, oxytocin, acetylcholine and barium chloride of vas deferens uterus und fundus strip was studied comparatively in hepatectomized and sarcoma-45, sarcoma-M1, Walker carcinosarcoma and Zajdela ascites hepatoma bearing rats. The contractile response to monoamines and oxytocin was considerably lower or absent at certain periods after hepatectomy or tumour grafting. Effects of biogenic amine antagonists were also substantially altered. The response to isoproterenol, acetylcholine and barium chloride remained unchanged. Apparently a selective alteration of a response of visceral smooth muscles mediated through alpha-adrenergic and D-serotonin receptors occurred not only during the tumour growth but also in the case of active (extensive) proliferation of the normal tissue.
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PMID:[The monoaminergic receptors of the internal organs in rats with a tumor and after partial hepatectomy]. 217 98

Our recent published studies suggest that angiotensin II (AII), generated and retained intracellularly, enhances growth of H4-II-E-C3 rat hepatoma cells, an average of 33%. Proliferation conferred by introduction of a plasmid [ Ang(-S)Exp/pSVL ] encoding a signal sequence-depleted angiotensinogen [Ang(-S)Exp] into these cells (which we have shown possess ACE and renin mRNAs) is mediated, at least in part, by enhanced PDGF-A chain mRNA production and protein secretion. The mitogenic effect is inhibited by losartan suggesting that it involves AII interaction with an AT(1)-like receptor. Introduction of anti-AII antibodies into the medium of these transfected cells has no effect upon growth of the cells, suggesting that AII is retained by the cells and that intracellular AII is growth stimulatory. In the present study, we sought to further characterize the intracellular localization and mode of action of Ang(-S)Exp. Consistent with our expectations, we now show that a fusion product of Ang(-S)Exp with green fluorescent protein [Ang(-S)Exp/EGFP], generated from an expression plasmid, is abundant and primarily cytoplasmic. Wild-type angiotensinogen/EGFP, in contrast, is only detectable following a cold-block (which acts to enhance folding-kinetics and slow secretion) and is largely restricted to the secretory pathway. We further show, using semi-quantitative RT/PCR that the long isoform of PDGF mRNA is elevated in Ang(-S)Exp transfected cells and in AII-treated naive cells but not in losartan-treated Ang(-S)Exp transfected cells. We identify C-terminal amidation recognition sites within the long-form protein (that are not present in the short-form) and show that these cells possess PAM (amidating enzyme precursor) and carboxypeptidase E mRNAs (the corresponding proteins of which are sufficient for amidation). Inhibitors of amidation inhibit growth of naive and Ang(-S)Cntr/ pSVL -transfected cells (2.6-fold for phenylbutenoic acid and 3.5-fold for disulfiram treatment) but more profoundly inhibit growth of Ang(-S)Exp/pSVL -transfected cells (6.7-fold for phenylbutenoic acid and 13-fold for disulfiram). In conclusion, these data confirm that signal sequence-depleted Ang(-S)Exp is retained within cells and is largely cytoplasmic. Because C-terminal amidation is absolutely required for full biological potency of a number of peptide hormones (including oxytocin, gastrin and calcitonin), we postulate that growth effects of both intracellular AII and exogenous AII can be conferred by PDGF long-form, possibly through an amidation-dependent mechanism.
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PMID:Intracellular angiotensin II increases the long isoform of PDGF mRNA in rat hepatoma cells. 1243 51

Emerging data indicate that the nervous system plays an important role in carcinogenesis. However, more studies are required to help further elucidate the mechanisms involved in the neural regulation of carcinogenesis. Some recent findings describing the neural regulatory mechanisms of action in prostate cancer, pancreatic cancer and hepatocellular carcinoma are discussed, with a focus on the sympathetic, parasympathetic, and sensory neuronal elements of the nervous system. Norepinephrine, which is released by the sympathetic nervous system and binds to the beta-adrenergic receptor, regulates cellular responses in both normal and tumor cells. It has also been shown that the destruction of sensory neurons can prevent or at least slow pancreatic cancer. Cortisol, the main stress hormone, is also discussed and how it could potentially be involved in hepatocellular carcinoma development. The importance of studying other signaling molecules in the nervous system, such as oxytocin and its receptor, the oxytocin receptor, and how they might be involved in carcinogenesis when aberrantly expressed is highlighted. This is an area of study which clearly needs further investigation. A clearer understanding of the detailed mechanisms of how the nervous system is involved in carcinogenesis could potentially aid in the identification of novel biomarkers and development of novel preventative and therapeutic strategies in various cancers.
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PMID:Emergence of neural regulatory mechanisms in carcinogenesis. 3152 43