Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The examination of the regulation of the system of 3'-5' cyclic nucleotide monophosphates has only begun in cancer tissues. In human cancers, these studies are notably non-existent. However, in animal cancers, especially the Morris hepatomas, enough data has been gathered that, while risky, certain trends seem to begin to appear. Cyclic AMP is constant or lowered, while cyclic GMP is elevated in the fast growing hepatomas. Regulation of adenylate cyclase by protein hormones is reduced, while regulation by epinephrine may be increased. Binding of glucagon is decreased in the fast growing hepatomas. Guanylate cyclase, while being predominantly cytoplasmic in the normal liver, is predominantly membrane bound in the tumors. The liver enzyme is also readily stimulated by several chemical carcinogens. The cyclic GMP phosphodiesterases are decreased in these tumors; while the cAMP phosphodiesterases are increased. Although the cyclic nucleotide dependent protein kinases (histone as substrate) are altered in the hepatomas, observations of unique cyclic nucleotide binding proteins or cAMP independent protein kinases in cancer tissues may be of even greater significance for the development of or the maintenance of the neoplastic state of cells.
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PMID:Cyclic nucleotide metabolism in solid tumor tissues. 2 89

1. Guanylate cyclase activity was determined in homogenates of guinea-pig islets of Langerhans by measurement of the conversion of [alpha-(32)P]GTP into cyclic [(32)P]GMP, the reaction products being separated on columns of neutral alumina. 2. The pH optimum of the enzyme was 7.3; it showed a requirement for bivalent cations, the effectiveness of the cations tested being Mn(2+)>>Ca(2+)>Mg(2+). 3. About 70% of enzyme activity was sedimented by centrifugation at 105000g for 60min; activity was increased 2.3-fold by treatment of homogenates with 0.1% Triton X-100. 4. Guanylate cyclase activity of homogenates was increased by acetylcholine, secretin or pancreozymin, but was inhibited by adrenaline, noradrenaline or ATP. Insulin, glucagon, prostaglandins E(1) or E(2), glucose, F(-), diazoxide or glibenclamide were ineffective. 5. Determination of cyclic GMP amounts in islets by radioimmunoassay showed a basal concentration of 2.0pmol/mg of protein, which was increased by incubation of the islets in the presence of acetylcholine or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, but was unaffected by glucose. 6. Dibutyryl cyclic GMP had significant stimulatory effects on rates of insulin biosynthesis in isolated rat islets of Langerhans. 7. These results suggest a possible role for cyclic GMP in the regulation of insulin biosynthesis and secretion.
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PMID:Regulation of guanylate cyclase in guinea-pig islets of Langerhans. 415 94