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)

1. The adenylate cyclase in Trypanosoma brucei is located in the plasma membrane. 2. A partial kinetic analysis of the properties of the enzyme revealed a Km for ATP of 1.75 mM and a Km for Mg2+ of 4mM. 3. At low concentrations, Mg2+ activated the enzyme directly in addition to its effect of lowering the concentration of inhibitory free ATP species. 4. At high concentrations, Mg2+ inhibited the enzyme. Furthermore, the enzyme was inhibited at any Mg2+ concentration if the concentration of ATP exceeded that of Mg2+. 5. The opposing effects of Mg2+ at low and high concentrations would be consistent with more than one binding site for Mg2+ on the enzyme. 6. A study of the patterns of product inhibition revealed little or no effect of 3':5'-cyclic AMP, but a profound inhibition by pyrophosphate, which was competitive with respect to ATP (Ki 0.135 mM). This result suggests that the substrate-binding domain on T. brucei adenylate cyclase interacts mainly with the triphosphate portion of the ATP molecule. 7. The enzyme activity was unaffected by the usual mammalian enzyme effectors glucagon, adrenaline, adenosine, GTP and guanyl-5'-yl imidodiphosphate. 8. The enzyme was not activated by fluoride, instead a powerful inhibition was found. The enzyme was also inhibited by relatively high concentrations of Ca2+ (1 mM).
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PMID:Adenylate cyclase in bloodstream forms of Trypanosoma (Trypanozoon) brucei sp. 3 75

1. Adenylate cyclase (EC 4.6.1.1) activity was characterized in human liver, and its subcellular distribution compared with that of three other potential enzyme markers of the pericellular membrane: leucine aminopeptidase (EC 3.4.11.1), gamma-glutamyltransferase (EC 2.3.2.2) and 5'-nucleotidase (EC 3.1.3.5). Although these three enzyme activities were detected in each of the subcellular fractions studied, 85% of the total adenylate cyclase activity was found in the 1000 g pellet ('nuclear' fraction) with a threefold increase in specific activity as compared with the homogenate. No adenylate cyclase activity existed in the 150 000 g supernatant fraction. 2. In the 'nuclear' fraction, adenylate cyclase activity was increased in a dose-dependent fashion by glucagon with a half-maximal stimulation at 10 nmol/l and a maximal four- to seven-fold increase at 1 mumol/l. Catecholamines activated adenylate cyclase 2.5- to three-fold, with an order of potency (protokylol greater than isoprenaline greater than adrenaline greater than noradrenaline) typical of a beta 2-adrenoreceptor. Prostaglandin E1 and NaF also stimulated cyclase two- and four-fold respectively. Insulin, serotonin, dopamine, thyroid-stimulating hormone and ACTH had no effect. Adenosine provoked a weak inhibition at 0.1 mmol/l. Finally guanosine triphosphate and 5'-guanylyl imidodiphosphate induced a marked increase in basal activity, four- and eight-fold respectively, but both reduced the relative increase in enzyme activity due to glucagon or adrenaline. 3. Cyclase from foetal liver (12--16 weeks old) and cirrhotic adult liver appeared to behave similarly to that from normal liver; however, foetal cyclase was more active, and cirrhotic enzyme less active than normal adult liver. Both systems responded to catecholamines via a beta 2-adrenoreceptor. 4. These results validate the use of rat liver adenylate cyclase as a tool for pharmacological and physiological studies.
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PMID:The adenylate cyclase system in human liver: characterization, subcellular distribution and hormonal sensitivity in normal or cirrhotic adult, and in foetal liver. 4 65

Particulate fractions of myocardium taken from spontaneously hypertensive rats (SHR) contained an adenylate cyclase system that was less responsive than normotensive Wistar Kyoto rats to norepinephrine, isoproterenol (mixed beta-agonist), salbutamol (beta 2-agonist), dobutamine (beta 1-agonist), dopamine, histamine, and glucagon. Addition of 5'-guanylylimidodiphosphate to the SHR myocardial preparation again yielded a lessened sensitivity to all agents except norepinephrine, dopamine, and histamine. Chronic treatment of SHR with clonidine and a high dose of propranolol produced a cardiac enzyme that was insensitive to activation by norepinephrine. Similar treatment with a low dose of propranolol did not alter myocardial responses to norepinephrine.
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PMID:Alterations in myocardial adenylate cyclase in spontaneously hypertensive rats. 4 30

The hormonal responsiveness of plasma membrane-bound enzymes (Na-+-K-+)-ATPase and adenylate cyclase has been investigated in normal and regenerating rat liver. (Na-+-K-+)-ATPase basal activity is not affected by surgery and only slightly affected by partial hepatectomy; its response to epinephrine and cyclic AMP is decreased only 15 h after hepatectomy. Adenylate cyclase activity of plasma membranes from untreated animals is stimulated by parathyroid hormone and thyroxine; partial hepatectomy increased basal activity as well as the stimulation exerted by the aforementioned hormones, when glucagon and epinephrine sensitivity is essentially unaltered.
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PMID:Hormone responsiveness of plasma membrane-bound enzymes in normal and regenerating rat liver. 12 2

1. Six rat liver plasma-membrane subfractions of different density and morphological, enzymic and chemical properties were prepared from homogenates by a combination of differential, rate-zonal and density-gradient centrifugation. They consisted of three vesicular 'light' subfractions of density 1.12-1.13 and three 'heavy' subfractions of density 1.16-1.18 containing membrane strips and intercellular junctions. 2. All six subfractions contained a basal adenylate cyclase activity. One of the 'light' subfractions that showed the highest glucagon-stimulated adenylate cyclase activity was identified as deriving form the blood-sinusoidal face of the hepatocyte. This subfraction, unlike the others, was contaminated by Golgi components, as indicated by its morphological properties and the presence of galactosyl- and sialyl-transferase activities. 3. All the six subfractions showed high activities of the following plasma-membrane marker enzymes: 5'-nucleotidase, alkaline phosphodiesterase (nucleotide pyrophosphatase), alkaline phosphatase, leucine naphthylamidase and Mg2+-activated adenosine triphosphatase. A 'light' subfraction that showed the highest specific activities of all the above marker enzymes, but lacked a glucagon-stimulated adenylate cyclase activity, was identified as deriving from the bile-canalicular face of the hepatocyte. 4. The 'heavy' subfractions, which showed generally the lowest activities of the above plasma-membrane enzyme markers, and were characterized by the presence of desmosomes and gap junctions, were taken to originate from the contiguous faces of the hepatocyte. 5. The protein composition of the six subfractions was generally similar, as shown by polyacrylamide-gel electrophoresis. Differences in the amounts of various protein and glycoprotein bands among the subfractions correlated with their morphology, enzymic composition and sialic acid content. 6. Hormonal and histochemical evidence supporting the identification of a bile-canalicular subfraction, a blood-sinusoidal subfraction and contiguous-face subfractions is discussed.
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PMID:Functional polarity of the rat hepatocyte surface membrane. Isolation and characterization of plasma-membrane subfractions from the blood-sinusoidal, bile-Canalicular and contiguous surfaces of the hepatocyte. 12 84

Some effects of salts on the adenylate cyclase of partially purified plasma membranes from rat liver have been studied. Under conditions where cyclic adenosine 3':5'-monophosphate formation was linear with respect to time and protein concentration, the enzyme was stimulated 3- to 6-fold by 10 mM NaF, 10- to 30-fold by 1 muM glucagon, 4- to 5-fold by 0.1 mM 5'-guanylylimidodiphosphate, and in the presence of 3 muM GTP, 2-fold by 10 mug/ml of prostaglandin E1. Various salts were found to stimulate basal activity slightly, but enhanced the response to NaF 3- to 4-fold, to glucagon 1.5- to 2-fold, to 5'-guanylylimidodiphosphate 2- to 3-fold, and to prostaglandin E1 1.5-fold. This enhancement was observed at maximally effective concentrations of each of the respective activators. Of the salts tested, NaN3 and the Na- or K-halides were most effective. Their action appeared to be due to the respective anions. Stimulation was detectable with 1.5 mM NaN3 or 3 mM NaCl and was maximal with 30 mM NaN3 or 60 mM NaCl. The stimulatory effect of NaN3 was not due to ATP-sparing, nor to an altered cyclic adenosine 3':5'-monophosphate recovery. It was independent of the chromatography and assay methods used, and was therefore not due to procedural artifact. Fluoride-stimulated cyclase activity was enhanced by salts to a greater degree than were 5'-guanylylimidodiphosphate-, glucagon-, or (prostaglandin E1 + GTP)-stimulated activities. The effects of NaN3 were not the result of significant changes in the enzyme's responses to GTP, which increased basal and glucagon-stimulated activities but inhibited F--stimulated activity. The effects of NaN3 were greater when cyclase was assayed with Mn2+ than with Mg2+. The facilitatory effect of NaN3 or NaCl on fluoride-stimulated adenylate cyclase activity was partially reversible as was the stimulatory effect of fluoride in the presence of NaN3. Enhancement of hormonal stimulation by NaN3 was also demonstrable with cardiac and adipose tissue adenylate cyclase. However, NaN3 did not stimulate detergent-dispersed adenylate cyclases from either liver plasma membranes or brain. The data suggest that stimulation of adenylate cyclase by salts may require the added presence of other stimulatory agents and an intact membrane structure.
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PMID:Liver membrane adenylate cyclase. Synergistic effects of anions on fluoride, glucagon, and guanyl nucleotide stimulation. 12 55

The adenylate cyclase activity from a rat liver plasma membrane preparation was inhibited by low concentrations (1-10 muM) of the mercurial diuretic mersalyl. Complete inhibition was obtained with 0.1 mM mersalyl. Similar effects were observed whether the adenylate cyclase preparation was assayed in the presence of 10 muM GTP, 0.1 muM glucagon, 10 mM NaF or without any addition. The effect of mersalyl was not due to inhibition of the regenerating system present in the incubation medium, since the effect of mersalyl was preserved and even enhanced in its absence. The inhibition brought about by mersalyl was due to both a decrease of the maximal velocity of the reaction and of the affinity of the enzyme for the substrate. It was immediate, and irreversible spontaneously, but it was reversed by the simultaneous additions of 2-mercaptoethanol, in a dose-dependent fashion. Other -SH reagents were found to have an effect equal to, or lower than, that of mersalyl. Mersalyl had no effect upon Mg2+-ATPase, although it inhibited the (Na+-K+) activated ATPase. Since mersalyl is known to be a 'non-penetrant' reagent, it is postulated that a catalytically important, mercurial-sensitive, part of adenylate cyclase is at the surface of the plasma membrane. This view is supported by the following facts: (a) mersalyl acted with a similar dose-response curve upon an intact as well as a detergent-dispersed cyclase preparation while no effect was observed upon a solubilized Mg2+-ATPase preparation; (b) a covalent p-chloromercuribenzoate-Sephadex preparation (but not its supernatant) inhibited the cyclase from intact membranes. It is proposed that mercurial derivatives, by their relative specificity of action (no effect on Mg2+-ATPase), can serve as useful probes in the elucidation of the multicomponent structure of the cyclase system.
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PMID:Adenylate cyclase from rat-liver plasma membrane: inhibition by mersalyl and other mercurial derivatives. 12 56

Changes in activities of plasma membrane enzymes during liver regeneration may be related to the maintenance of hepatic function or to the regulation of cell proliferation. Plasma membranes were isolated from rat livers at various times after partial hepatectomy, and the specific activities of alkaline phosphatase, (Na+ + K+)-ATPase, leucine aminopeptidase, 5'-nucleotidase, and adenylate cyclase (basal and with glucagon or epinephrine) were measured. Alkaline phosphatase and (Na+ + K+)-ATPase activity increased 3.6-fold and 2-fold respectively, during the first 48 h after partial hepatectomy. The time of onset and duration of change suggest that these increases in activity are involved in the maintenance of bile secretion. Decreases in leucine aminopeptidase activity at 48--108 h and in 5'-nucleotidase activity at 12--24 h were observed, which may be involved in the restoration of protein and accumulation of RNA. The basal activity of adenylate cyclase increased after partial hepatectomy. The response of adenylate cyclase to epinephrine showed a transitory increase between 36 and 108 h after surgery, while the response to glucagon was decreased by approximately 50% at all time points through 324 h after surgery. These changes in the hormone responsiveness of adenylate cyclase are similar to those previously observed in fetal and preneoplastic liver.
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PMID:Changes in plasma membrane enzyme activities during liver regeneration in the rat. 14 24

Genetically obese (ob/ob) mice, mice that became obese after treatment with gold thioglucose, and lean animals were studied in the euthyroid state, after induction of hypothyroidism, and after treatment with triiodothyronine. The activity of glycerol 3-phosphate dehydrogenase (sn-glycerol-3-phosphate:(acceptor) oxidoreductase; EC 1.1.99.5] was reduced in the livers from hypothyroid animals and was increased by treatment with triiodothyronine in all groups. The activity of the ouabain-suppressible sodium- and potassium-dependent ATPase (ATP phosphohydrolase; EC 3.6.1.3) was increased by triiodothyronine and reduced by hypothyroidism in the lean and gold thioglucose-treated obese animals. In the obese (ob/ob) mice, on the other hand, treatment with triiodothyronine did not increase the activity of this enzyme, which remained at the level found in hypothyroid animals. This enzymatic activity was reduced in both liver and kidney. Adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] activity in liver membranes, however, was similar in all three groups of mice. This enzyme complex was activated by glucagon and was unaffected by treatment with thyroid hormones. The lack of a thyroid-dependent ouabain-suppressible (Na(+) + K(+))-ATPase in the tissues of the obese (ob/ob) mouse could explain most, if not all, of the abnormalities that have been described in this animal.
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PMID:An enzymatic defect in the obese (ob/ob) mouse: loss of thyroid-induced sodium- and potassium-dependent adenosinetriphosphatase. 14 80

Heparin was found to be the most potent inhibitor of rat ovarian luteinizing hormone-sensitive adenylate cyclase (I50 = 2 microgram/ml) when compared to other naturally occurring glycosamin oglycans. This inhibition was also apparent when this enzyme was stimulated by follicle-stimulating hormone or prostaglandin E2. Heparin was also found to inhibit glucagon-sensitive rat hepatic adenylate cyclase, and the prostaglandin E1-sensitive enzyme from rat ileum and human platelets. In contrast, heparin stimulated the dopamine sensitive adenylate cyclase from rat caudate nucleus. The sulfated polysugar dextran sulfate exerts similar effects on adenylate cyclase activity of the rat ovary and was shown to inhibit hormone binding to rat ovarian plasma membrane in a manner similar to that exerted by heparin. In contrast to heparin, dextran sulfate inhibited dopamine-sensitive adenylate cyclase from rat caudate nucleus.
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PMID:Modulation of adenylate cyclase activity by sulfated glycosaminoglycans. II. Effects of mucopolysaccharides and dextran sulfate on the activity of adenylate cyclase derived from various tissues. 15 57


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