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)

The adenosine analogue 9-(Tetrahydro-2-furyl)adenine, SQ 22536, inhibited adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity of crude membrane preparations from catfish (Ictalurus melas) and rat isolated hepatocytes in a non-competitive manner. The IC50s were reduced in the presence of NaF. SQ 22536 reduced the activity of adenylate cyclase also in the presence of increasing concentrations of GTP, as well as Mg++ and Mn++. In the presence of catecholamines (epinephrine, norepinephrine, isoproterenol, phenylephrine) SQ 22536 reduced their activating effect on adenylate cyclase in both catfish and rat membranes. SQ 22536 also inhibited the effect of glucagon (0.1 microM) on rat membrane cyclase activity.
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PMID:Inhibition of adenylate cyclase of catfish and rat hepatocyte membranes by 9-(tetrahydro-2-furyl)adenine (SQ 22536). 166 44

The effects of an adenosine analog, N6-phenyl-isopropyl-adenosine (PIA), on the glucagon-stimulated adenylate cyclase activity in rat hepatic membranes were studied. Adenosine at high concentrations (greater than 10 microM) has been reported exclusively to inhibit the adenylate cyclase via intracellular P-sites of the hepatic membrane. The stimulation by glucagon of the enzyme was attenuated by nanomolar concentrations of PIA in the presence of low concentrations (less than 1.0 microM) of GTP, indicating the effect of the guanine nucleotide inhibitory system (Ni). This inhibition by PIA required the presence of sodium chloride and was antagonized with isobutyl methylxanthine, an antagonist for the extracellular R-site receptors. The inhibitory effects of PIA disappeared and reversed into a stimulatory phase with increasing concentrations of GTP, suggesting the presence of a stimulatory (Ns) and an inhibitory (Ni) guanine nucleotide system of the enzyme in the action of the adenosine. PIA concentrations over a micromolar were observed to stimulate the enzyme activity in a GTP-dependent manner, indicating the presence of the stimulatory receptor (A2 or Ra) coupled to the Ns. These results suggest that receptors for adenosine of the inhibitory type (A1 or Ri) and the stimulatory type (A2 or Ra) are present on the rat hepatic membrane, showing multiple controls of the adenylate cyclase system, depending on the cellular concentrations of GTP and/or sodium chloride.
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PMID:Multiple controls by adenosine receptors on the adenylate cyclase in the rat hepatic membrane. 169 17

Hepatocarcinogenesis was initiated in rats with diethylnitrosamine (DEN) followed by a selection with 2-acetylamino-fluorene (2-AAF). Portacaval shunt was then performed in order to promote tumor development. Control rats were not submitted to the initiation--selection protocol and were sham-operated. In control rats, adenylate cyclase activity from crude liver membranes was stimulated 7- to 8-fold by maximal doses of glucagon (10(-6) M) or guanyl-5'-yl-imidophosphate [Gpp(NH)p] (10(-3) M), and 17-fold by a maximal (10(-5) M) dose of forskolin. Guanosine-5'-O-(2-thiodiphosphate) inhibited the response to forskolin (-38%) and to low doses of glucagon (-50%). The initiation--selection protocol increased the activity in basal conditions and in response to various stimuli. The portacaval shunt did not modify the activity of the enzyme with respect to basal activity or the response to glucagon. It significantly decreased the response to Gpp(NH)p (-45%) and to forskolin (-27%). The initiation--selection protocol increased the basal activity of the enzyme (+150%) and its response to Gpp(NH)p (+300%). When tumors developed, the activity of the cyclase further increased (+200%) and an inhibitory effect of GTP on the hormone-stimulated enzyme appeared (-40%). From these results, it is concluded that the promotion of hepatocarcinogenesis by portacaval shunt is coupled with modifications in the activity of adenylate cyclase in response to glucagon and guanylnucleotides.
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PMID:Adenylate cyclase activity in crude liver membranes during chemical hepatocarcinogenesis in portacaval shunted rats. 174 14

Receptors for vasoactive intestinal peptide (VIP) in membranes from rat seminal vesicle were examined using 125I-labeled VIP as ligand. The receptor binding was rapid, reversible, saturable, specific, and dependent on temperature and membrane concentration. At 15 degrees C, the stoichiometric data suggested the presence of two classes of VIP receptors with Kd values of 0.54 and 44.4 nM and binding capacities of 73 and 1,065 fmol VIP/mg membrane protein, respectively. The interaction showed a high degree of specificity, as suggested by competition experiments with various peptides structurally related to VIP as follows: helodermin was 10 times, secretin 30 times, and rat growth hormone-releasing factor 300 times less potent than VIP, whereas glucagon did not recognize VIP receptors in concentrations of up to 10 microM. The binding of 125I-VIP to membranes was sensitive to the presence of GTP in the incubation medium in a dose-dependent manner. To characterize the molecular weight of these VIP receptors, 125I-VIP was covalently bound to membranes from rat seminal vesicle using dithiobis(succinimidyl propionate); sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized receptor revealed the presence of a specific component with a molecular mass of 47,000 Da as estimated in denaturing conditions. These findings, together with the known presence of VIP-containing nerves in the seminal vesicle, suggest a direct physiological role for this peptide in this accessory gland of the male genital tract.
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PMID:Characterization of vasoactive intestinal peptide receptors in rat seminal vesicle. 184 88

Several hormones, including insulin, glucagon, and glucocorticoids, regulate the expression of the rate-limiting gluconeogenic enzyme, phosphoenolpyruvate carboxykinase [GTP: oxaloacetate carboxy-lyase (transphosphorylating); EC 4.1.1.32; PEPCK] in liver. In this report we demonstrate that retinoic acid (RA) also regulates PEPCK expression by inducing a 3-fold increase in the rate of transcription of the PEPCK gene. A RA response element located between -468 and -431 in the PEPCK promoter mediates a 7-fold increase in expression of a chimeric construct containing the basal PEPCK promoter ligated to the chloramphenicol acetyltransferase reporter gene. This element confers RA responsiveness through the heterologous thymidine kinase promoter and functions relatively independent of position and orientation. An 18-base-pair core sequence (-451 to -434) (i) mediates an effect of RA on PEPCK gene expression and contains motifs found in two other RA response elements; (ii) corresponds to AF1, an accessory factor element that is an integral component of the complex glucocorticoid response unit in the PEPCK gene promoter; (iii) is in a region involved in the developmental expression of the PEPCK gene; and (iv) shows homology to elements involved in the tissue-specific regulation of genes, including the hepatic apolipoprotein genes and the alpha 1-antitrypsin gene.
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PMID:A retinoic acid response element is part of a pleiotropic domain in the phosphoenolpyruvate carboxykinase gene. 184 96

Incubation of Candida albicans yeast cells with human luteinizing hormone (hLH), human chorionic gonadotrophin (hCG) or glucagon produced a significant rise in cAMP total levels. The effect of these hormones in permeabilized cells of the fungus produced a 2-3 fold increase in the Mg2+, GTP-dependent adenylyl cyclase activity as well as full activation of the cAMP-dependent protein kinase (PKA) activity. These results indicate that the interaction of the mammalian hormones with the fungus triggered the cAMP activation cascade in a similar way to that found in higher eukaryotic organisms.
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PMID:Activation of the cAMP cascade by steroidogenic hormones and glucagon in the pathogenic fungus Candida albicans. 185 67

The hydrodynamic behavior of G alpha s, the alpha subunit of the stimulatory guanine nucleotide-binding regulatory protein (G protein), in octyl glucoside extracts of rat liver membranes was investigated. As was previously shown for G proteins similarly extracted from brain synaptoneurosomes, G alpha s behaved as polydisperse structures with S values higher than that of heterotrimeric G proteins. At concentrations of guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]) greater than 100 microM, incubation with membranes led to smaller structures having S values in the range of 4-5 S. Incubation of liver membranes with glucagon also caused a marked increase in structures having these S values; glucagon action required the presence of low concentrations of GTP[gamma S] (maximal, 10 microM), was rapid (within 10 sec), and was not observed with vasopressin, angiotensin II, or glucagon-(19-29). When G alpha s in its membrane-bound form was [32P]ADP-ribosylated by cholera toxin and the treated membranes were extracted with octyl glucoside, greater than 35% of the labeled G alpha s was found in material that sedimented through sucrose gradients and contained relatively low levels of immunoreactive G alpha s. Glucagon selectively converted the apparently large molecular weight structures to the 4-5 S structures in the presence of GTP[gamma S], even at 1 mM (the maximal effect of the nucleotide alone), when incubated with the toxin-treated membranes. These findings suggest that the glucagon receptor selectively interacts with polymer-like structures of G alpha s and that activation by GTP[gamma S] results in disaggregation. The role of the beta and gamma subunits of G proteins in the hormone-induced process is not clear since the polymer-like structures extracted with octyl glucoside are devoid of beta and gamma subunits.
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PMID:Glucagon induces disaggregation of polymer-like structures of the alpha subunit of the stimulatory G protein in liver membranes. 190 89

Liver plasma membranes prepared from genetically diabetic (db/db) mice expressed levels of Gi alpha-2, Gi alpha-3 and G-protein beta-subunits that were reduced by some 75, 63 and 73% compared with levels seen in membranes from lean animals. In contrast, there were no significant differences in the expression of the 42 and 45 kDa forms of Gs alpha-subunits. Pertussis toxin-catalysed ADP-ribosylation of membranes from lean animals identified a single 41 kDa band whose labelling was reduced by some 86% in membranes from diabetic animals. Cholera toxin-catalysed ADP-ribosylation identified two forms of Gs alpha-subunits whose labelling was about 4-fold greater in membranes from diabetic animals compared with those from lean animals. Maximal stimulations of adenylyl cyclase activity by forskolin (100 microM), GTP (100 microM), p[NH]ppG (100 microM), NaF (10 mM) and glucagon (10 microM) were similar in membranes from lean and diabetic animals, whereas stimulation by isoprenaline (100 microM) was lower by about 22%. Lower concentrations (EC50-60 nM) of p[NH]ppG were needed to activate adenylyl cyclase in membranes from diabetic animals compared to those from lean animals (EC50-158 nM). As well as causing activation, p[NH]ppG was capable of eliciting a pertussis toxin-sensitive inhibitory effect upon forskolin-stimulated adenylyl cyclase activity in membranes from both lean and diabetic animals. However, maximal inhibition of adenylyl cyclase activity in membranes from diabetic animals was reduced to around 60% of that found using membranes from lean animals. Pertussis toxin-treatment in vivo enhanced maximal stimulation of adenylyl cyclase by glucagon, isoprenaline and p[NH]ppG through a process suggested to be mediated by the abolition of functional Gi activity. The lower levels of expression of G-protein beta-subunits, in membranes from diabetic compared with lean animals, is suggested to perturb the equilibria between holomeric and dissociated G-protein subunits. We suggest that this may explain both the enhanced sensitivity of adenylyl cyclase to stimulation by p[NH]ppG in membranes from diabetic animals and the altered ability of pertussis and cholera toxins to catalyse the ADP-ribosylation of G-proteins in membranes from these two animals.
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PMID:Determination of G-protein levels, ADP-ribosylation by cholera and pertussis toxins and the regulation of adenylyl cyclase activity in liver plasma membranes from lean and genetically diabetic (db/db) mice. 193 44

The binding sites to glucagon with KD 10(-9) M in rat and chicken isolated hepatocytes and with KD 10(-7) M in chicken hepatocytes only where revealed. The first, but not the second binding sites where decreased in their affinity by the adding of GTP nonhydrolyzing analogue Gpp(NH). Glucagon activated the cAMP accumulation in rat and chicken hepatocytes in dose-depended manner. The dose-response curve being plateau after maximum in rats and decreased in chicken. Glucagon inserted an inhibiting effect when occupying chicken-specific sites of binding with KD 10(-7) M. The nature of these binding sites and mechanism of glucagon inhibiting effect on the cAMP accumulation are discussed.
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PMID:[Glucagon receptor binding and its effect on the cAMP level in isolated rat and chicken hepatocytes]. 196 55

Crude plasma membranes were prepared from the liver of control rats or of rats submitted to an initiation by diethyl-nitrosamine and selection with 2-acetylaminofluorene and carbon tetrachloride (group IS) or of rats submitted to an initiation-selection protocol followed by a promotion with phenobarbital (group IS PB). In control rats, the diterpene forskolin and glucagon stimulated the activity of adenylate cyclase 6- to 7-fold. Guanosine-5'-O-(2-thiodiphosphate) (GDP beta S) inhibited the stimulation by both agents and the non-hydrolyzable GTP analog, guanyl-5'-yl-imidodiphosphate [Gpp(NH)p], potentiated the stimulatory effect of glucagon. In rats of the IS group, no modification of the activity of the liver cyclase was found, except for an increased response to forskolin and glucagon. In the IS PB group, for the rats without tumor, the only effect of adding phenobarbital was to increase the sensitivity of the cyclase to forskolin. In tumoral tissue, the response to Gpp(NH)p, glucagon and forskolin were increased when compared to the surrounding tissue. In contrast to the surrounding tissue, GDP beta S potentiated the stimulatory effect of forskolin. When the affinity of the glucagon receptors for the hormone was measured in binding experiments, no difference was observed among the rats of the various groups, except for a higher affinity in tumoral tissue. Similarly, GTP inhibited the binding of glucagon with the same potency in each group. It is concluded that during hepatocarcinogenesis, the sensitivity of the adenylate cyclase towards glucagon increases secondarily to a better binding of the hormone to its receptor and to an impairment of the inhibitory regulatory site.
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PMID:Adenylate cyclase activity in crude liver membranes during chemical hepatocarcinogenesis. 201 30


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