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

Glucagon and adrenaline exert their action upon the liver via the cyclic AMP synthetizing system located in the plasma membrane. The enzyme adenylate cyclase is further regulated by guanyl nucleotides. It has been recently shown that the rat liver plasma membrane system could respond to GTP by simultaneous increase in the cyclase activity in response to glucagon and by the dissociation of this hormone from its binding sites (1). Unambiguous relationship between the activating effect of GTP upon the cyclase and its action upon glucagon binding has not been determined yet (2). This problem was approached using the in vitro action of epinephrine as a model. When 1 to 100 muM GTP or DGP were added to rat liver plasma membranes isolated from adrenalectomized animals, they increased markedly the response of the cyclase system to epinephrine. These effects could be observed in the absence of an ATP-regenerating system and were mimicked by 5'-guanylyl diphosphonate; GTP and GDP were the most active compounds followed by ITP, CTP and by a series of guanyl derivatives. UTP, as well as guanosine, GMP, cyclic GMP and ppGpp were inactive. Guanyl nucleotides did not increase the affinity of the cyclase system for the activating hormones, but enhanced the affinity for ATP-Mg and also the Vmax of the reaction. Finally, GTP, ATP, CTP, UTP but not GDP displaced epinephrine bound to plasma membranes by a mere chelation phenomenon. It is concluded that 1) guanyl nucleotides do not act primarily by influencing the binding of hormones to the membranes; 2) they act directly upon the catalytic subunit of the cyclase; 3) the low concentrations of GTP required for its action strongly suggest that this nucleotide plays a role in the physiological regulation of the intrahepatic cyclic AMP level.
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PMID:[Role of guanidylic nucleotides in the adenylate cyclase activity of the rat liver]. 120 15

Glucagon and N6,O2'-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) inhibit net glucose utilization, lactate plus pyruvate accumulation and fatty acid synthesis by isolated hepatocytes prepared from meal-fed rats. A crossover in the metabolite profile of the glycolytic intermediates occurs between fructose-6-phosphate and fructose-1,6-bisphosphate, suggesting either inhibition of phosphofructokinase or activation of fructose diphosphatase, or both. Direct assay of the enzymes in cell-free extracts of the hepatocytes indicates that dibutyryl cyclic AMP inhibits phosphofructokinase but has no effect upon fructose diphosphatase. The assay for phosphofructokinase was modified by the use of ITP in place of ATP for the phosphate donor as the ATP-linked assay is complicated by an apparent time-dependent activation of the enzyme. These findings strongly suggest that cyclic AMP inhibition of phosphofructokinase explains in part cyclic AMP inhibition of aerobic glycolysis and lipogenesis by rat liver hepatocytes.
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PMID:Glucagon and N6,O2'-dibutyryl adenosine 3':5'-monophosphate inhibition of lipogenesis and phosphofructokinase activity of hepatocytes from meal-fed rats. 625 34

Specific binding sites for vasoactive intestinal peptide were characterized in plasma membranes from rat intestinal epithelial cells. At 30 degrees C, the interaction of 125I-labelled peptide with intestinal membranes was rapid, reversible, specific and saturable. At equilibrium, the binding of 125I-labelled peptide was competitively inhibted by native peptide in the 3 . 10(-11)--3 . 10-(7) M range concentration. Scatchard analysis of binding data suggested the presence of two distinct classes of vasoactive intestinal peptide binding sites: a class with a high affinity (Kd = 0.28 nM) and a low capacity (0.8 pmol peptide/mg membrane protein) and a class with a low affininty (Kd = 152 nM) and a high capacity (161 pmol peptide/mg membrane protein). Secretin competitively inhibited binding of 125I-labelled peptide but its potency was 1/1000 that of native peptide. Glucagon and the gastric inhibitory peptide were ineffective. The guanine nucleotides, GTP and Gpp(NH)p inhibited markedly the interaction of 125I-labelled peptide with its binding sites, by increasing the rate of dissociation of peptide bound to membranes. The other nucleotides triphosphate tested (ATP, ITP, UTP, CTP) were also effective in inhibiting binding of 125I-labelled peptide to membranes but their potencies were 1/100--1/1000 that of guanine nucleotides. The specificity and affinity of the vasoactive intestinal peptide-binding sites in plasma membranes prepared from rat intestinal epithelial cells, which is in agreement with an adenylate cyclase highly sensitive to the peptide recently characterized in these membranes (Amiranoff, B., Laburthe, M., Dupont, C. and Rosselin, G. (1978) Biochim. Biophys. Acta 544, 474--481) further argue for a physiological role of the peptide in the regulation of intestinal epithelial function.
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PMID:Characterization of specific binding sites for vasoactive intestinal peptide in rat intestinal epithelial cell membranes. 735 Sep 25