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)

Rat liver plasma membranes contain (Ca2+-Mg2+)-ATPase sensitive to inhibition by both glucagon and Mg2+. We have previously shown that Mg2+ inhibition is mediated by a 30,000-dalton inhibitor, originally identified as a membrane-bound protein. In fact, this inhibitor is also present in the 100,000 X g supernatant of the total liver homogenate. Its purification was achieved from this fraction by a combination of ammonium sulfate washing, gel filtration, and cationic exchange chromatography. N-Ethylmaleimide (NEM) treatment caused the inactivation of the purified inhibitor, which suggested that this protein possesses at least one NEM-sensitive sulfhydryl group essential for its activity. Treatment of the liver plasma membranes with NEM resulted in a 2- and 5-fold decrease in the affinity of the (Ca2+-Mg2+)-ATPase for glucagon and Mg2+, respectively, while the basal enzyme activity remained unchanged. This effect of NEM was concentration-, pH-, and time-dependent, optimal conditions being obtained by a 60-min treatment of plasma membranes with 50 mM NEM, at pH 7 and at 4 degrees C. The presence of 0.5 mM Mg2+ during NEM treatment of the plasma membranes prevented NEM inactivation. Reconstitution experiments showed that addition of the purified inhibitor to NEM-treated plasma membranes restored the inhibitions of the (Ca2+-Mg2+)-ATPase by both magnesium and glucagon. It is proposed that the (Ca2+-Mg2+)-ATPase inhibitor not only confers its sensitivity of the liver (Ca2+-Mg2+)-ATPase to Mg2+, but also mediates the inhibition of this system by glucagon.
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PMID:The inhibitor of liver plasma membrane (Ca2+-Mg2+)-ATPase. Purification and identification as a mediator of glucagon action. 316 Jul 1

We have purified an ATP-dependent protease with protein-dependent ATPase activity from bovine adrenal cortex mitochondria to near homogeneity. The subunit molecular weight is 108,000 and the enzyme appears to be a hexamer with approximately identical subunits. Based on the experiments using various nucleoside triphosphates and their related compounds, it is concluded that hydrolysis of the high-energy bond in nucleoside triphosphates is not an absolute requirement for proteolysis. Nucleotide specificity of this enzyme varies, depending on the protein or peptide substrates used. When casein was the substrate, ATP and dATP were quite effective, but other nucleotides were not. When insulin and angiotensinogen were used as substrate, ATP, other nucleoside triphosphates, ADP, inorganic triphosphate, pyrophosphate, and phosphate were effective. One of the cleaving linkages hydrolyzed by this enzyme was revealed to be the Leu-Leu bond of angiotensinogen. However, the specificity appears to be broad in view of the hydrolysis pattern of glucagon.
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PMID:Adrenal cortex mitochondrial enzyme with ATP-dependent protease and protein-dependent ATPase activities. Purification and properties. 390 33

Chlorpromazine (3 x 10(-4)M) prevents the stimulation of adenyl cyclase activity in thyroid membranes produced by thyrotropin and prostaglandin, ACTH stimulation of adenyl cyclase in adrenal tissue, and glucagon- and epinephrine-stimulation of adenyl cyclase activity in liver. Baseline activity is unaffected. Parathyroid hormone stimulation of kidney preparations was not inhibited under these conditions. At chlorpromazine concentrations >3 x 10(-4)M F(-)-stimulated cyclase activity of thyroid and adrenal tissue was increased. Other phenothiazines, trifluoperazine, and prochlorperazine, have similar effects on thyrotropin and F(-)-stimulated cyclase activity of thyroid. Na(+)- K(+)-dependent ATPase of thyroid is also inhibited by chlorpromazine. Since thymol causes a similar dissociation of hormone- and F(-)-stimulated adenyl cyclase, it is concluded that the surface properties of these agents best account for their effects on adenyl cyclase.
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PMID:Inhibition of hormone-sensitive adenyl cyclase by phenothiazines. 431

We describe an abrupt increase (at 32 degrees ) in the energy of activation for the reaction of hepatic adenylyl cyclase in the presence of glucagon or epinephrine. This increase is not seen in the presence of fluoride, prostaglandin E(1), or 1-propanol, or in the absence of cyclase stimulators. The change in energy of activation found with hormones is abolished by 1-propanol. This change does not represent differences in hormone or substrate binding at different temperatures, but seems to reflect interactions among elements of the cyclase stimulation sequence. Similar changes in energy of activation were not observed for alkaline phosphatase, cyclic AMP-phosphodiesterase, 5'-nucleotidase, or ouabain-sensitive ATPase. Since the mole fraction of cholesterol in liver membranes is sufficiently high to preclude a phase change in bulk membrane lipids, our observation suggests either that cyclase is restricted to cholesterol-poor membrane regions or that the change in its energy of activation is largely restricted to protein components of the cyclase apparatus. The data are compatible with fundamental differences in the stimulation process(es) for the hormones (glucagon and epinephrine) as compared with those for fluoride and prostaglandin E(1).
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PMID:A temperature-sensitive change in the energy of activation of hormone-stimulated hepatic adenylyl cyclase. 435 55

The main purpose of the present study was to examine the mechanism and regulation of hepatic bile acid-independent canalicular bile production. The experiments were performed on fasted, anesthetized intact cats and rats with acute bile fistulae, on perfused rat livers and with isolated liver plasma membranes from these species. The effect of insulin and glucagon on bile production was examined. The possible role of Na, K-ATPase for bile production was studied by administration of inhibitors (ouabain, vanadate) of this enzyme. Also the effect of insulin and glucagon on hepatic Na, K-ATPase was examined. Finally, the literature describing this field is reviewed and discussed in relation to the findings of the present experiments. It is concluded, that a part of the canalicular bile is produced independently of bile acid secretion and that the formation of this fraction can be stimulated by insulin and glucagon via a direct action of the hormones on the liver. It seems that interaction between the two canalicular fractions of bile formation is possible. The mechanism of bile acid-independent canalicular bile formation is still unsettled and conclusive evidence for the direct involvement of hepatic Na, K-ATPase in the secretion of this fraction is lacking.
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PMID:Mechanism and regulation of hepatic bile production. With special reference to the bile acid-independent canalicular bile formation. 608 41

A high affinity Ca2+-stimulated, Mg2+-dependent ATPase (Ca2+-Mg2+-ATPase) was identified in microsomes and plasma membrane vesicles isolated from rat hepatocytes. The distribution of this enzyme was similar to that of the plasma membrane marker enzymes alkaline phosphodiesterase and 5'-nucleotidase. The Ca2+-Mg2+-ATPase had an apparent half-saturation constant of approximately 75 nM for Ca2+. After incubation of rat hepatocytes with 25 nM vasopressin for 3 min, the activity of Ca2+-Mg2+-ATPase was decreased 15-30%. The effect of vasopressin on the activity of this enzyme was near maximal after incubating hepatocytes with vasopressin for only 15 sec. The concentration of vasopressin needed for half-maximal inhibition of this enzyme in hepatocytes was approximately 6 nM. Treatment of the hepatocytes with 10 microM phenylephrine caused about a 10% decrease in ATPase activity while 10 nM glucagon or 200 microU/ml insulin did not affect the enzyme. These findings suggest that inhibition of the Ca2+-Mg2+-ATPase activity may be part of the mechanism by which vasopressin and alpha-adrenergic agonists elevate cytosolic Ca2+ in hepatocytes.
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PMID:Regulation of Ca2+-Mg2+-ATPase activity in hepatocyte plasma membranes by vasopressin and phenylephrine. 613 76

The ATP-dependent calcium transport in plasma membrane vesicles prepared from rat liver was inhibited by 0.1 to 10 microM glucagon. Inhibition of the high affinity (Ca2+-Mg2+)-ATPase was observed concomitantly. This effect was neither mimicked by cyclic AMP nor by dibutyryl cyclic AMP. A study of the structure-activity relationships of six glucagon derivatives demonstrated the specificity of glucagon action since only one or two analogs markedly altered the (Ca2+-Mg2+)-ATPase activity. The study also demonstrated the total absence of correlation between adenylate cyclase activation and (Ca2+-Mg2+)-ATPase inhibition induced by these glucagon derivatives. The decrease in the maximal velocities induced by glucagon of both calcium transport and (Ca2+-Mg2+)-ATPase activity were related to a reduction in the rate of dephosphorylation of the Ca-dependent phosphorylated intermediate of the enzyme. This phosphorylated intermediate was characterized as a 32P-labeled 110,000-dalton protein which accumulated to 50 to 150% over the basal level in the presence of glucagon. The present results demonstrate a novel aspect of the role of glucagon as a calcium-mobilizing agent.
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PMID:Inhibition by glucagon of the calcium pump in liver plasma membranes. 614 15

1. Ruthenium Red-insensitive Ca2+ transport in the mouse ascites sarcoma 180/TG is enriched in a 'heavy' microsomal fraction (microsomes) sedimented at 35 000 g for 20 min. The subcellular distribution of this Ca2+ transport differed from that of Ruthenium Red-sensitive Ca2+ transport and (Na+ + K+)-dependent ATPase activity, but was similar to that of glucose 6-phosphatase. 2. The affinity of this transport system for 'free' Ca2+ is high (Km approx. 6 microM) and that for MgATP somewhat lower (Km approx. 100 microM). Ca2+ transport by the tumour microsomes, by contrast with that by liver microsomes, was greatly stimulated by low concentrations of P1. 3. Although incubation of intact ascites cells with glucagon led to an increase in intracellular cyclic AMP, no stable increase in the initial rate of Ca2+ transport in the subsequently isolated 'heavy' microsomes could be detected as in similar experiments carried out previously with rat liver cells. Reconstitution experiments suggest that a deficiency exists in the tumour microsomal membrane such that an action of glucagon that is normally present in rat liver microsomes is not evoked.
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PMID:Ruthenium red-insensitive calcium transport in ascites-sarcoma 180/TG cells. 617 24

The energy requirement for protein breakdown in Escherichia coli results from an ATP requirement for the function of protease La, the product of the lon gene. This novel serine protease contains an ATPase activity that is essential for proteolysis. ATP and protein hydrolysis show the same Km for ATP (30-40 muM) and are affected similarly by various inhibitors, activators, and ATP analogs. Vanadate inhibited ATP cleavage and caused a proportionate reduction in casein hydrolysis, and inhibitors of serine proteases reduced ATP cleavage. Thus, ATP and protein hydrolysis appear to be linked stoichiometrically. Furthermore, ATP hydrolysis is stimulated two- to threefold by polypeptides that are substrates for the protease (casein, glucagon) but not by nonhydrolyzed polypeptides (insulin, RNase). Unlike hemoglobin or native albumin, globin and denatured albumin stimulated ATP hydrolysis and were substrates for proteolysis. It is suggested that the stimulation of ATP hydrolysis by potential substrates triggers activation of the proteolytic function.
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PMID:Protease La from Escherichia coli hydrolyzes ATP and proteins in a linked fashion. 621 87

Several groups of investigators have shown that treatment of rats with glucagon produces an increase in the adenine nucleotide content of hepatic mitochondria. It has been suggested that this enlarged pool of exchangeable nucleotides may be responsible for several of glucagon's stimulatory effects on mitochondrial functions by accelerating the transport of adenine nucleotides across the inner mitochondrial membrane. This hypothesis was tested by loading rat liver mitochondria in vitro with adenine nucleotides to supranormal levels. This procedure did result in stimulation of several metabolic and bioenergetic functions including pyruvate carboxylation, uncoupler-dependent ATPase, and succinic dehydrogenase activity but not formation of citrulline. However, a sham loading that did not increase the nucleotide content of the mitochondria was essentially as effective as the loading procedure in stimulating those functions assayed. Mitochondria, loaded in vitro with supranormal levels of adenine nucleotides, were shown to have an enlarged pool of exchangeable nucleotides. This exchange was atractyloside sensitive, but the rate of exchange was only slightly increased as a consequence of enlargement of the pool. Similarly, mitochondria isolated from glucagon-treated rats showed no increase in the rate of exchange, although the exchangeable pool was increased. There was no correlation between the rate of nucleotide exchange and the rate of the uncoupler-dependent ATPase.
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PMID:Elevated intramitochondrial adenine nucleotides and mitochondrial function. 622 97


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