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 lecturer recalls the discovery of glucagon receptors in liver cell membranes, the role of the adenylate cyclase-AMPc system, until recent attempts at purification and isolation of this receptor. He then reviews successively, the problems of estimation, specificity of the interaction, the effects of purine and pyrimidine nucleotides on glucagon receptor interaction, etc. The importance of the two nucleotides GTP and ATP in activation of adenylate cyclase is emphasized. The VIP receptors ("vasoactive intestinal peptide") and secretin receptors are also discussed. In some ways, they resemble glucagon receptors. The possible consequences of these discoveries arethen discussed.
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PMID:[Glucagon receptors]. 18 43

The adenylate cyclase responses of the human GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors to TRH, LH-RH, biogenic amines, peptides hormones, PGE1 and rat median eminence extract (MEE) have been examined. Out of 4 GH producing pituitary adenomas obtained from patients with active acromegaly at hypophysectomy two were stimulated by TRH, two by LH-RH, three by norepinephrine, one by dopamine, four by PGE1 and none by serotonin. Glucagon stimulated the adenylate cyclase in one of three and MEE in both of two tested. The positive responses of paradoxical GH release after TRH and/or LH-RH before surgery in these patients coincidentally related to the response of adenylate cyclase of each pituitary adenoma. There seems, however, to be no consistent correlation between the adenylate cyclase responses to biogenic amines and the GH release after L-Dopa or 5-hydroxytroptophan tested. The adenylate cyclase of a pituitary adenoma from case of Cushing's disease was stimulated by LH-RH, norepinephrine glucagon and MEE but not by TRH. Plasma levels of ACTH, beta-MSH and cortisol increased after LH-RH but not after TRH in this patient before hypophysectomy. The adenylate cyclase of two ectopic ACTH producing tumors (gastric carcinoid and malignant thymoma) was activated by TRH, LH-RH, norepinephrine, epinephrine, serotonin, PGE1 and MEE. These results indicate the presence of multiple hormone receptors in GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors, and suggest that the paradoxical GH or ACTH release after TRH and/or LH-RH injection in acromegaly and Cushing's syndrome might be caused by an alteration of the cellular membrane receptors of the pituitary adenomas.
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PMID:Adenylate cyclase of GH and ACTH producing tumors of human: activation by non-specific hormones and other bioactive substances. 19 Feb 56

Age-related decreases of hormone-sensitive adenylate cyclase activities of rat fat cell plasma membranes (ghosts) have been recently described. Glucagon-sensitive activity was completely lost between 1 and 6 mo, an interval in which fat cell size increases rapidly, while decreased activation by ACTH was gradual over the entire life span of the animal (24 mo), and epinephrine-sensitive enzyme diminished modestly and only during senescence. In the present studies an attempt was made by restricting food intake to assess the importance of changing cell size in the age-related alterations of hormone-sensitive enzyme activities. Enzyme activities were determined before restriction and at monthly intervals for 3 mo for the unstimulated enzyme (basal) and in the presence of maximally stimulating concentrations of glucagon, ACTH, epinephrine, and fluoride. Activities were calculated per milligram ghost protein or per cell. Restriction of food intake for 3 mo starting at 1 or 12 mo produced fat cells equal in size to those of 5-wk-old animals fed ad lib. In young animals restricted for 1 mo, hormone-stimulated activity expressed as fold increase (stimulated/basal) was not merely maintained as the cells were prevented from enlarging, but was enhanced two to three times over the initial values with all three hormones. With continued restriction epinephrine-sensitive activity remained two times increased. Glucagon and ACTH responses subsequently decreased, but even by 3 mo of restriction, responses to the latter hormones, although declining, were still 1.5-3 times greater than the unrestricted controls, regardless of whether activity was expressed as total activity per milligram ghost protein or per cell, or as fold-increase. In the young animals, basal and fluoride-sensitive activities after a 3-mo restriction were unchanged or had decreased only slightly, depending on the base line used. Dietary restriction of adult animals for 3 mo, in contrast to the results in the young, did not increase total hormone-stimulated activity but rather produced either 0% (per milligram protein) or 25% decrease (per cell) for epinephrine-sensitive enzyme, 25 or 50% decrease of ACTH response, and 40 or 60% decreases of basal- and fluoride-stimulated activities. Expression of activities of restricted adults as fold-increase (stimulate/basal) showed an "increase of responsiveness" for all three hormones, but this was a reflection of the marked decrease of basal activity. Nonetheless, the restricted adults showed significant restoration of a small amount of glucagon-sensitive activity (1.8-fold over basal). These results indicate that cell size, per se, is not a dominant factor affecting hormone-responsive adenylate cyclase under conditions of dietary restriction...
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PMID:Enhanced activity of hormone-sensitive adenylate cyclase during dietary restriction in the rat: dependence on age and relation to cell size. 19 Feb 68

The present study was designed to identify the physicochemical, immunologic, and biologic properties of the immunoreactive glucagon (IRG) moieties of canine gastric fundus and to compare them with those of the canine pancreas. Acid-alcohol extracts of the gastric fundus and pancreas of dogs were subjected to Bio-Gel P-10 chromatography, The elution profiles of extracts of both organs revealed IRG peaks in the Mr = 2,000 3,500, and 9,000 zones; in the gastric extracts, a void volume peak was also present. On the basis of Sephadex G-150 rechromatography and sucrose density gradient ultracentrifugation the latter IRG was estimated to have a Mr = 65,000. Incubation of fundic IRG65,000 in 8 M urea failed to alter its elution position. Its pI was 6.4, while fundic IRG3,500 had a pI of 6.15 and pancreatic glucagon 6.25. Fundic IRG9,000 had a pI of 4.5 and pancreatic IRG9,000 4.65. Dilution curves of these three fundic and two pancreatic IRGs were parallel to crystalline beef-pork glucagon. The glycogenolytic activity of fundic IRG3,500 and IRG65,000, measured in the isolated rat liver system, was not different from that of immunoequivalent amounts of dog pancreatic glucagon or crystalline beef-pork glucagon. Both fundic and pancreatic IRG9,000 were devoid of glycogenolytic activity and lacker adenylate cyclase stimulating activity and 125I-glucagon displacing activity when tested on partially purified rat liver membranes. Fundic IRG65,000, however, stimulated adenylate cyclase and displaced 125I-glucagon to the same degree as immunoequivalent amounts of pancreatic glucagon. Fundic IRG3,500 was more active than pancreatic glucagon in stimulating adenylate cyclase activity. This was not clearly attributable to differences in binding to liver cell membranes.
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PMID:Properties of immunoreactive glucagon fractions of canine stomach and pancreas. 19 45

Treatment of rat liver plasma membranes with various commercial preparations of crude collagenase from Clostridium histolyticum at concentrations as low as 1 mug/ml, resulted in activation of the adenylate cyclase system. Maximal activation occurred at 50 to 100 mug/ml of collagenase, and promoted a 2- to 3-fold increase in the basal activity as well as in the activities stimulated by catecholamines, glucagon, fluoride, or GTP. This was due to an increase in the maximal velocity of the cyclizing reaction without any increase in the affinity of the enzyme for its substrate. Treatment of plasma membranes with crude collagenase did not induce gross structural modifications as judged by electron microscopic examination. 5'-Nucleotidase activity was slightly inhibited and ATPase activity remained unaffected. The stimulatory substance was nondialyzable, thermolabile, and inhibited by both EDTA and -SH reagents, thus appearing to be a protein. The following observations suggest the effects observed were due to other protease(s) present in crude collagenase: (a) only crude collagenase was active on liver adenylate cyclase: treatment with purified collagenase from C. histolyticum or from Achromobacter iophagus gave no stimulation; (b) the stimulatory activity was irreversible since washing of the membranes after treatment was without effect; (c) crude collagenase contained no lecithinase or sphingomyelinase activity under our conditions of adenylate cyclase assay; (d) after chromatography on Sephadex G-100, the activator appeared as a peak in the 30,000-dalton region and was clearly separated from the collagenase and clostripain peaks, but coincident with elastolytic and caseinolytic activities; (e) the effect of crude collagenase could be prevented by addition of elastin in vitro and was mimicked by purified elastase from hog pancreas. It remains to be seen whether the effects observed result from an increase in the catalytic constant of adenylate cyclase, or an unmasking of new catalytic sites.
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PMID:Proteolytic activation of rat liver adenylate cyclase by a contaminant of crude collagenase from Clostridium histolyticum. 19 49

Basal activity and hormonal responsiveness of the adenylate cyclase-adenosine 3',5'-monophosphate system were examined in premalignant liver from rats chronically fed the hepatic carcinogen DL-ethionine, and these data were correlated with endogenous levels of plasma glucagon. By 2 weeks basal hepatic cyclic AMP levels, determined in tissues quick-frozen in situ, were 2-fold higher in rats ingesting ethionine than in the pair-fed control. Enhanced tissue cyclic AM content was associated with an increase in the adenylate cyclase activity of whole homogenates of fresh liver from rats fed ethionine (68 +/- 5 pmol cyclic AMP/10 min per mg protein) compared to control (48 +/- 4). Cyclic AMP-dependent protein kinase activity ratios were also significantly higher (control, 0.38 +/- 0.04; ethionine 0.55 +/- 0.05) and the percent glycogen synthetase activity in the glucose 6-phosphate-independent form was markedly reduced (control, 52 +/- 7%; ethionine, 15 +/- 1.5%) in the livers of ethionine-fed rats compared to the controls, suggesting that the high total hepatic cyclic AMP which accompanied ethionine ingestion was bilogically effective. These changes persisted throughout the 38 weeks of drug ingestion. Immunoreactive glucagon levels, determined in portal venous plasma, were 8-fold higher than control after 2 weeks of the ethionine diet (control, 185 +/- 24 pg/ml; ethionine, 1532 +/- 195). Analogous to the changes in hepatic parameters, plasma glucagon levels remained elevated during the entire period of drug ingestion until the development of hepatomas. The hepatic cyclic AMP response to a maximal stimulatory dose of injected glucagon was blunted in vivo in ethionine-fed rats (control, 14 -fold increase over basal, to 8.63 +/- 1.1 pmol/mg wet weight; ethionine, 4.6-fold rise over basal, to 5.42 +/- 0.9). Reduced cyclic AMP responses to both maximal and submaximal glucagon stimulation were also evident in vitro in hepatic slices prepared from rats fed the drug, and the reduction was specific to glucagon. Absolute or relative hepatic cyclic AMP responses to maximally effective concentrations of protaglandin E1 or isoproterenol in hepatic slices from ethionine-fed rats were greater than or equal to those observed in control slices. Parallel alterations in hormonal responsiveness were observed in adenylate cyclase activity of whole homogenates of these livers, implying that the changes in cyclic AMP accumulation following hormone stimulation were related to an alteration in cyclic AMP generation in the premalignant tissue. In view of the recognized hepatic actions of glucagon and the desensitization of adenylate cyclase which can occur during sustained stimulation of the liver with this hormone, the endogenous hyperglucagonemia that accompanies ethionine ingestion could play a role in the pathogenesis of both the basal alterations in hepatic cyclic AMP metabolism and the reduced responsiveness to glucagon observed in liver from rats fed this carcinogen.
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PMID:Hyperglucagonemia and altered responsiveness of hepatic adenylate cyclase-adenosine 3',5'-monophosphate system to hormonal stimulation during chronic ingestion of DL-ethionine. 19 13

[3-Iodo-Tyr2]oxytocin (MIOT), [3,5-diiodo-Tyr2]oxytocin (DIOT), [3-iodo-Tyr2,Lys8]vasopressin (MILVP), [3,5-diiodo-Tyr2,Lys8]vasopressin (DILVP), [3-iodo-Tyr2,Arg8]vasopressin (MIAVP), and [3,5-diiodo-Tyr2,Arg8]vasopressin (DIAVP) were synthesized by iodination of the respective hormones, pruified, and characterized. All the monoiodo hormones had to be freshly prepared prior to bioassays, since on storage they gave rise to hormonal-like biological activity. The biological activities of these iodo analogues were measured in an adenylate cyclase assay employing neurohypophyseal hormone (NHH) sensitive bovine renal medullary membranes, and/or the rat oxytocic assay. In the cyclase assay, DIOT, DILVP, and DIAVP were inactive as agonists or antagonists. MIOT shows no agonistic activity in the renal cyclase system and uterus, but is a weak reversible inhibitor of oxytocin (OT) in both systems. When MIOT (10(-4) M) was preincubated with renal membranes for 10 min at 37 degrees C before addition of OT, it behaved as a noncompetitive inhibitor of NHH-stimulated adenylate cyclase. MILVP and MIAVP appear to be partial agonists with Km (half maximal response) 3 X 10(-6) and 3 X 10(-7) M, respectively, as determined in the cyclase assay. Upon preincubation with renal medullary membranes, MILVP (10(-6) M) behaves as a more potent noncompetitive inhibitor of OT than MIOT. Accordingly, iodo derivatives of NHH do not exhibit sufficient affinity to serve an specific ligands to measure OT, LVP, or AVP receptors in the uterus and kidney. Study of the specificity of inhibition produced by MIOT revealed that this analogue does not act selectively upon NHH receptors. Thus, MIOT modified adenylate cyclase systems which do not have NHH receptors, e.g., the PTH-sensitive adenylate cyclase in bovine renal cortex and the glucagon-sensitive adenylate cyclase in rat liver. DIOT, DILVP, and DIAVP were subjected to catalytic tritiation (employing carrier free tritium) and were converted to [3H]OT (25, 31, and 25 Ci/mmol), [3H]LVP (26 and 23 Ci/mmol), and [3H]AVP (17 Ci/mmol), respectively. These tritiated ligands have been successfully used to measure NHH receptor sites both in kidney and uterine membranes as described in other studies.
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PMID:Iodinated neurohypophyseal hormones as potential ligands for receptor binding and intermediates in synthesis of tritiated hormones. 19 53

Murine 3T3-L1 fibroblasts enter a differentiation program subsequent to prolonged maintenance in the confluent state and develop into adipocytes. The hormone sensitivity of adenylate cyclase and the physiological responsiveness to insulin were compared in 3T3-L1 preadipocytes and adipocytes. The following observations, comprising several distinct categories of hormone responsiveness, were made. (a) (2.5 micronM) isoproterenol stimulated adenylate cyclase 15-fold in adipocyte homogenates, but only 2.5-fold in preadipocyte preparations, suggesting a considerable magnification in beta-adrenergic responsiveness during development. (b) A totally new control element, adrenocorticotropic hormone responsiveness, was incorporated into the adenylate cyclase system of the adipocytes. (c) Sensitivity to prostaglandin E1 was observed in both preadipocytes and adipocytes, but no change in responsiveness could be detected in the differentiated cells. (d) Glucagon-sensitive adenylate cyclase could not be detected in either preadipocytes or adipocytes. (e) Both preadipocytes and adipocytes possess considerable insulin binding activity, but near physiological levels of insulin stimulate the conversion of glucose to CO2 and lipid only in the differentiated cells.
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PMID:Acquisition of increased hormone sensitivity during in vitro adipocyte development. 19 37

Human peripheral lymphocytes were broken in a Dounce homogenizer and subcellular fractions enriched in plasma membranes or microsomal particles and mitochondria were isolated by centrifugation through a discontinuous sucrose gradient. Various agents that promote cyclic AMP accumulation in intact lymphocytes were compared in their ability to stimulate adenylate cyclase activity in the individual fractions. Plasma-membrane-rich fractions that were essentially free of other subcellular particles as judged by electron microscopy and marker enzyme measurements responded to fluoride, but weakly or not at all to prostaglandin E1 and other prostaglandins. Microsomal and mitochondrial-rich fractions responded markedly to both prostaglandin E1 and fluoride. In some, but not all, experiments phytohaemagglutinin produced a modest increase in enzyme activity in plasma-membrane-rich fractions. Catecholamines, histamine, parathyrin, glucagon and corticotropin produced little or no response. In the absence of theophylline, adenosine (1-10 micronM) stimulated basal enzyme activity, although at higher concentrations the responses to prostaglandin E1 and fluoride were inhibited. GTP (1-100 micronM) and GMP(5-1000 micronM) respectively inhibited or stimulated the response to fluoride, whereas the converse was true with prostaglandin E1.
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PMID:Adenylate cyclase activity in lymphocyte subcellular fractions. Characterization of non-nuclear adenylate cyclase. 19 77

The sensitivity to hormones of the fat cell adenylate cyclase system was tested in uremic rats and in pair-fed control animals. Basal enzyme activities averaged 1.25 nmoles of cAMP formed per mg protein per 15 min in controls compared to 1.30 nmoles cAMP/mg protein/15 min in fat cell ghosts obtained from uremic rats. NaF caused an approximately 4-fold stimulation of enzyme activities in both systems. It was shown that parathyroid hormone should be included amongst the hormones which act as stimulators of the enzyme system. The responsiveness of the rat fat cell adenylate cyclase system towards saturating concentrations of ACTH, glucagon, epinephrine and parathyroid hormone was not altered in the presence of chronic renal failure.
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PMID:Unchanged hormone sensitivity of rat fat cell adenylate cyclase in uremia. 19 63


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