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)

Myocardial triacylglycerol hydrolysis is subject to product inhibition. After hydrolysis of endogenous triacylglycerols, the main proportion of the liberated fatty acids is re-esterified to triacylglycerol, indicating the importance of fatty acid re-esterification in the regulation of myocardial triacylglycerol homoeostasis. Therefore, we characterized phosphatidate phosphohydrolase (PAP) and diacylglycerol acyltransferase (DGAT) activities, enzymes catalysing the final steps in the re-esterification of fatty acids to triacylglycerols in the isolated rat heart. The PAP activity was mainly recovered in the microsomal and soluble cell fractions, with an apparent Km of 0.14 mM for both the microsomal and the soluble enzyme. PAP was stimulated by Mg2+ and oleic acid. Oleic acid, like a high concentration of KCl, stimulated the translocation of PAP activity from the soluble to the particulate (microsomal) fraction. Myocardial DGAT had an apparent Km of 3.8 microM and was predominantly recovered in the particulate (microsomal) fraction. Both enzyme activities were significantly increased after acute streptozotocin-induced diabetes, PAP from 15.6 +/- 1.1 to 28.1 +/- 3.6 m-units/g wet wt. (P less than 0.01) and DGAT from 2.23 +/- 0.11 to 3.01 +/- 0.11 m-units/g wet wt. (P less than 0.01). In contrast with diabetes, low-flow ischaemia during 30 min did not affect PAP and DGAT activity in rat hearts. Perfusion with glucagon (0.1 microM) during 30 min did not affect total PAP activity, but changed the subcellular distribution. More PAP activity was recovered in the particulate fraction. DGAT activity was lowered by glucagon treatment from 0.37 +/- 0.03 to 0.23 +/- 0.02 m-unit/mg of microsomal protein (P less than 0.05). The role of PAP and DGAT activity and PAP distribution in the myocardial glucose/fatty acid cycle is discussed.
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PMID:Properties of phosphatidate phosphohydrolase and diacylglycerol acyltransferase activities in the isolated rat heart. Effect of glucagon, ischaemia and diabetes. 216 15

GTP, GTP-gamma-S and Gpp(NH)p produced a significant activation of Mg2(+)-dependent adenylyl cyclase in permeabilized cells of Candida albicans. This activation was inhibited by GDP-beta-S. Maximal stimulation (4-6 fold) was obtained when Mg2+ and GTP-gamma-S were added during permeabilization. The guanine nucleotide-stimulated activity could be further activated by glucagon in a dose dependent manner being the maximal stimulation (4-5 fold) attained at 10(-6) M glucagon. Addition of the hormone to yeast cells incubated under conditions conducive to produce germ tubes blocked hyphal development and promoted multibudded cell morphology.
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PMID:A guanine nucleotide-sensitive, glucagon-stimulated adenylyl cyclase in Candida albicans: effect of glucagon on cell morphology. 218 26

Indirect evidence has indicated that the carbohydrate moieties of the glycoprotein hormones are involved in the activation of the receptor-adenylyl cyclase system of reproductive tissues. In the present study, we have isolated the glycopeptides (GP) from human chorionic gonadotropin (hCG), the alpha-subunit of hCG, fetuin, and bovine gamma-globulin (b gamma G). These along with a number of synthetic oligosaccharides were tested for their ability to inhibit adenylyl cyclase (AC). There was less than 0.001% cross-reactivity of the GP from hCG, hCG alpha, fetuin, and b gamma G when tested in a double-antibody hCG radioimmunoassay or rat corpora lutea radioreceptor assay. The GP of fetuin, b gamma G, and the synthetic oligosaccharides did not inhibit AC activity of 2000 g corpora lutea membranes when coincubated with 100 ng of hCG/mL (ED50). However, when the GP of hCG and hCG alpha were included with intact hCG, there was a dose-related inhibition. Inhibition of cyclase activity was enhanced when the hCG GP were desialylated. This occurred without a change in the lag time of hCG activation which was calculated to be 1-1.5 min. Changing the concentration of ATP and Mg2+ did not affect the inhibitory effects of the hCG alpha GP on hCG-stimulated AC activity. Inhibition by hCG GP followed uncompetitive kinetics. The inhibition by the GP of hCG seems to be restricted to the LH/hCG-stimulatable AC system because the same dosage of hCG GP which inhibited the rat luteal AC system did not have any effect on the rat hepatocyte AC system when coincubated with glucagon or on NaF-stimulated activity in luteal membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of adenylyl cyclase activity in rat corpora luteal tissue by glycopeptides of human chorionic gonadotropin and the alpha-subunit of human chorionic gonadotropin. 241 22

The presence of adenosine receptors coupled to adenylate cyclase in rat heart sarcolemma is demonstrated in these studies. Heart sarcolemma was isolated by the hypotonic shock-Lithium bromide treatment method. This preparation contained negligible amounts (2-4%) of contamination by other subcellular organelles such as mitochondria, sarcoplasmic reticulum, and myofibrils as verified by electron microscopic examination. In addition this preparation was also devoid of endothelial cells, since angiotensin-converting enzyme activity was not detected in this preparation. N-Ethylcarboxamide adenosine (NECA), L-N6-phenylisopropyladenosine (PIA), and adenosine N'-oxide (Ado N'-oxide) were all able to stimulate adenylate cyclase in heart sarcolemma, but not in crude homogenate, with an apparent Ka of 3-7 microM. The activation of adenylate cyclase by NECA was dependent on the concentrations of metal ions such as Mg2+ or Mn2+. The maximal stimulation was observed at lower concentrations of the metal ions (0.2-0.5 mM). At 5 mM Mg2+ or Mn2+, the stimulation by NECA was completely abolished. The stimulatory effect of NECA on adenylate cyclase was also dependent on guanine nucleotides and was blocked by 3-isobutyl-1-methylxanthine. In addition, 2'-deoxyadenosine showed an inhibitory effect on adenylate cyclase. The myocardial adenylate cyclase was also stimulated by beta-adrenergic agonists, dopamine and glucagon, and inhibited by cholinergic agonists such as carbachol and oxotremorine. The stimulation of adenylate cyclase by NECA was found to be additive with maximal stimulation obtained by epinephrine. These data suggest that rat heart sarcolemma contains adenosine (Ra), beta-adrenergic, dopaminergic, glucagon, and cholinergic receptors, and the stimulation of adenylate cyclase by epinephrine and adenosine occurs by distinctly different mechanism or adenosine and epinephrine stimulate different cyclase populations.
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PMID:Regulation of adenylate cyclase by adenosine and other agonists in rat myocardial sarcolemma. 241 61

The effect of heparin on the renal adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP) system was studied in vitro in renal cortical membrane preparations and in vivo on hormone-stimulated nephrogenous cAMP excretion. The heparin dose dependently inhibited basal and hormone-stimulated rat renal cortical AC activity. The heparin concentration causing 50% inhibition was 45 micrograms/ml for the basal activity and 33 and 85 micrograms/ml for the parathyroid hormone (PTH) and glucagon-stimulated activities, respectively. PTH- and glucagon-stimulated AC activity was inhibited by the non-antithrombotic heparinoid, N-acetylated N-disulfated heparin, but not by a structural analogue of heparin, dextran sulfate. Forskolin- and Mn2(+)-stimulated AC activity was also inhibited by heparin, while NaF stimulated activity was resistant to it. Increasing Mg2+ concentration did not affect the inhibition of basal and PTH-stimulated AC activity by heparin. The urinary excretion of nephrogenous cAMP was determined in parathyroidectomized rats treated with glucagon (group 1), glucagon and heparin (group 2), heparin alone (group 3) and control (group 4). Glucagon induced a significant increase in nephrogenous cAMP excretion. The urinary excretion of nephrogenous cAMP, however, was significantly lower in group 2 (receiving glucagon and heparin) than in group 1 (receiving glucagon alone). There were no significant changes in nephrogenous cAMP in groups 3 and 4. These results suggest that heparin is a potent inhibitor of renal AC in vivo and in vitro. Taken together, our data point out the catalytic unit of the AC system as the site of heparin interaction.
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PMID:Effect of heparin on cortical adenylate cyclase activity and on urinary excretion of 3',5'-adenosine monophosphate in rat. 248 35

Incubation of a hepatocyte particulate fraction with ATP and the isolated catalytic unit of cyclic AMP-dependent protein kinase (A-kinase) selectively activated the high-affinity 'dense-vesicle' cycle AMP phosphodiesterase. Such activation only occurred if the membranes had been pre-treated with Mg2+. Mg2+ pre-treatment appeared to function by stimulating endogenous phosphatases and did not affect phosphodiesterase activity. Using the antiserum DV4, which specifically immunoprecipitated the 51 and 57 kDa components of the 'dense-vesicle' phosphodiesterase from a detergent-solubilized membrane extract, we isolated a 32P-labelled phosphoprotein from 32P-labelled hepatocytes. MgCl2 treatment of such labelled membranes removed 32P from the immunoprecipitated protein. Incubation of the Mg2+-pre-treated membranes with [32P]ATP and A-kinase led to the time-dependent incorporation of label into the 'dense-vesicle' phosphodiesterase, as detected by specific immunoprecipitation with the antiserum DV4. The time-dependences of phosphodiesterase activation and incorporation of label were similar. It is suggested (i) that phosphorylation of the 'dense-vesicle' phosphodiesterase by A-kinase leads to its activation, and that such a process accounts for the ability of glucagon and other hormones, which increase intracellular cyclic AMP concentrations, to activate this enzyme, and (ii) that an as yet unidentified kinase can phosphorylate this enzyme without causing any significant change in enzyme activity but which prevents activation and phosphorylation of the phosphodiesterase by A-kinase.
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PMID:Activation and phosphorylation of the 'dense-vesicle' high-affinity cyclic AMP phosphodiesterase by cyclic AMP-dependent protein kinase. 254 54

The mammalian renal thick ascending limb of Henle (TAL) reabsorbs approximately 55% of the filtered magnesium; accordingly, it is the major segment involved in control of renal Mg balance. This review discusses recent evidence for passive and active transport of Mg through the paracellular and transcellular pathways of the TAL, respectively. The properties of these pathways provide a basis for understanding the factors influencing magnesium reabsorption and hormonal controls regulating Mg balance. Normally, Mg absorption is load dependent, whether delivery is altered by increasing luminal Mg concentration or increasing the flow rate into the thick ascending limb. In contrast to the luminal concentration, elevation of peritubular (plasma) Mg and Ca inhibit divalent cation absorption by mechanisms that are not entirely clear. Magnesium reabsorption in the TAL is also closely associated with NaCl absorption so that factors that influence NaCl also affect magnesium. Magnesium deficiency results in a specific and apparently intrinsic cellular adaptation to increase Mg absorption in the TAL. Our greatest understanding of hormonal controls for Mg absorption have come from recent studies using a "hormone deprived" animal model. Parathyroid hormone, calcitonin, glucagon, and antidiuretic hormone act through a common second messenger, adenosine 3',5'-cyclic monophosphate, to limit Mg excretion by enhancing active Mg transport in the TAL. The integrated actions of these hormones and possibly others provide a sensitive means of control. Clearly, recent observations, using in vivo and in vitro microperfusion studies, have altered our thinking of TAL function and indicate that Mg transport is sensitively and specifically controlled within this segment.
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PMID:Control of magnesium transport in the thick ascending limb. 264 45

The effects of glucagon on transepithelial Na+, Cl-, K+, Ca2+ and Mg2+ net fluxes were investigated in isolated perfused cortical (cTAL) and medullary (mTAL) thick ascending limbs of Henle's loop of the mouse nephron. Transepithelial ion net fluxes (JNa+, JCl-, JK+, JCa2+, JMg2+) were determined by electron probe analysis of the collected tubular fluid. Simultaneously the transepithelial voltage (PDte) and the transepithelial resistance (Rte) were recorded. In cTAL-segments (n = 8), glucagon (1.2 x 10(-8) mol.1-1) stimulated significantly the reabsorption of Na+, Cl-, Ca2+ and Mg2+: JNa+ increased from 204 +/- 20 to 228 +/- 23 pmol.min-1.mm-1, JCl- from 203 +/- 18 to 234 +/- 21 pmol.min-1.mm-1, JCa2+ from 0.52 +/- 0.13 to 1.34 +/- 0.30 pmol.min-1.mm-1 and JMg2+ from 0.51 +/- 0.08 to 0.84 +/- 0.08 pmol.min-1.mm-1.JK+ remained unchanged: 3.2 +/- 1.3 versus 4.0 +/- 1.9 pmol.min-1.mm-1. Neither PDte (16.3 +/- 1.5 versus 15.9 +/- 1.4 mV) nor Rte (22.5 +/- 3.0 versus 20.3 +/- 2.6 omega cm2) were changed significantly by glucagon. However, in the post-experimental periods a significant decrease in PDte and increase in Rte were noted. In mTAL-segments (n = 9), Mg2+ and Ca2+ transports were close to zero and glucagon elicited no significant effect. The reabsorptions of Na+ and Cl-, however, were strongly stimulated: JNa+ increased from 153 +/- 17 to 226 +/- 30 pmol.min-1.mm-1 and JCl- from 151 +/- 23 to 243 +/- 30 pmol.min-1.mm-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of glucagon on Na+, Cl-, K+, Mg2+ and Ca2+ transports in cortical and medullary thick ascending limbs of mouse kidney. 281 41

1. The matrix pyrophosphate (PPi) content of isolated energized rat liver mitochondria incubated in the presence of ATP, Mg2+, Pi and respiratory substrate was about 100 pmol/mg of protein. 2. After incubation with sub-micromolar [Ca2+], this was increased by as much as 300%. There was a correlation between the effects of Ca2+ on PPi and on the increase in matrix volume reported previously [Halestrap, Quinlan, Whipps & Armston (1986) Biochem. J. 236, 779-787]. Half-maximal effects were seen at 0.3 microM-Ca2+. 3. Coincident with these effects, the total adenine nucleotide content increased in a carboxyatractyloside-sensitive manner. 4. Incubation with 0.2-0.5 mM-butyrate induced similar but smaller effects on mitochondrial swelling and matrix PPi and total adenine nucleotide content. Addition of butyrate after Ca2+, or vice versa, caused Ca2+-induced mitochondrial swelling to stop or reverse, while matrix PPi increased 30-fold. 5. Addition of atractyloside or the omission of ATP from incubations greatly enhanced swelling induced by Ca2+ without increasing matrix PPi. 6. Swelling of mitochondria incubated under de-energized conditions in iso-osmotic KSCN was progressively enhanced by the addition of increasing concentrations of PPi (1-20 mM) or valinomycin. 7. In iso-osmotic potassium pyrophosphate swelling was slow initially, but accelerated with time. This acceleration was inhibited by ADP, whereas carboxyatractyloside induced rapid swelling. Swelling in other iso-osmotic PPi salts showed that the rate of entry decreased in the order NH4+ greater than K+ greater than Na+ greater than Li+, whereas choline, tetramethylammonium and Tris did not enter. It is suggested that the adenine nucleotide translocase transports small univalent cations when PPi is bound and that PPi can also be transported when the transporter is in the conformation induced by carboxyatractyloside. 8. It is concluded that Ca2+ and butyrate cause swelling of energized mitochondria through this effect of PPi on K+ permeability of the mitochondrial inner membrane. 9. Freeze-clamped livers from rats treated with glucagon or phenylephrine show 30-50% increases in tissue PPi. It is proposed that Ca2+-mediated increases in mitochondrial PPi are responsible for the increase in matrix volume and total adenine nucleotide content observed after hormone treatment.
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PMID:Liver mitochondrial pyrophosphate concentration is increased by Ca2+ and regulates the intramitochondrial volume and adenine nucleotide content. 282 49

The effects of Mg2+ or ethylenediaminetetraacetic acid (EDTA) on 125I-glucagon binding to rat liver plasma membranes have been characterized. In the absence of guanosine 5'-triphosphate (GTP), maximal binding of 125I-glucagon occurs in the absence of added Mg2+. Addition of EDTA or Mg2+ diminishes binding in a dose-dependent manner. In the presence of GTP, maximal binding occurs in the presence of 2.5 mM Mg2+ (EC50 = 0.3 mM) while EDTA or higher concentrations of Mg2+ diminish binding. Response to exogenous Mg2+ or EDTA depends on the concentration of Mg2+ in the membranes and may vary with the method used for membrane isolation. Solubilized 125I-glucagon-receptor complexes fractionate on gel filtration columns as high molecular weight, GTP-sensitive complexes in which receptors are coupled to regulatory proteins and lower molecular weight, GTP-insensitive complexes in which receptors are not coupled to other components of the adenylyl cyclase system. In the absence of GTP, 40 mM Mg2+ or 5 mM EDTA diminishes receptor affinity for hormone (from KD = 1.2 +/- 0.1 nM to KD = 2.6 +/- 0.3 nM) and the fraction of 125I-glucagon in high molecular weight receptor-Ns complexes without affecting site number (Bmax = 1.8 +/- 0.1 pmol/mg of protein). Thus, while GTP promotes disaggregation of receptor-Ns complexes, Mg2+ or EDTA diminishes the affinity with which these species bind hormone. In the presence of GTP, hormone binds to lower affinity (KD = 9.0 +/- 3.0 nM), low molecular weight receptors uncoupled from Ns.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Divalent cations regulate glucagon binding. Evidence for actions on receptor-Ns complexes and on receptors uncoupled from Ns. 283 83


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