Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Fast-frozen pectoralis muscle samples were taken from normal chickens (lines 200 and 412) and chickens having hereditary muscular dystrophy (line 304). The glycogen phosphorylase activity ratio (activity without AMP/activity with AMP) was significantly greater in dystrophic muscles (0.306 +/- 0.046) than it was in normal muscles (0.090 +/- 0.023). Glucagon treatment did not cause any changes in phosphorylase activity ratios. Isoproterenol treatment of both normal and dystrophic muscles raised the phosphorylase activity ratio of normal muscles to 0.446 +/- 0.054, which was not significantly different from that of the dystrophic muscles. The dystrophic muscles had significantly less glycogen than normal muscles (23.3 +/- 2.8 compared with 36.8 +/- 2.8 mumoles glucosyl units/g of muscle). There was no relationship of muscular dystrophy to total phosphorylase activity (measured in the presence of 1 mM AMP) and to glycogen synthase activities measured without and with glucose 6-phosphate. Normal muscles had 28% less cAMP and 49% less cGMP than dystrophic muscles, but these differences were eliminated by treatment of the chickens with glucagon.
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PMID:Glycogen cycle enzymes and cyclic nucleotides in avian muscular dystrophy. 624 56

Human CSF cyclic nucleotides do not distinguish manic-depresive patients or schizophrenic patients from controls, although a "high CSF cyclic AMP" subgroup of poor-prognosis schizophrenics is still under investigation. Neuroleptic therapy raises CSF cyclic GMP and lowers CSF cyclic AMP, at least in the responder subgroup of a clinically heterogeneous patient population when neuroleptics that are good adenylate cyclase inhibitors in vitro are used in the treatment. This is consistent with the concept that neuroleptic treatment in humans involves blockade of dopamine neurotransmission. Attempts to correlate the decline in CSF cyclic AMP concentration with clinical improvement may be important. Lithium treatment does not alter the level of CSF cyclic AMP, which probably derives largely from dopamine-related neurotransmission that lithium does not affect. However, the plasma cyclic AMP response to epinephrine is inhibited by lithium at therapeutic doses in vivo after chronic treatment. The lithium effect is somewhat specific in that the glucagon-stimulated rise in plasma cyclic AMP is not affected. The results in clinical experiments support the theory that norepinephrine-sensitive adenylate cyclase inhibition in brain is involved in lithium action. Research to attempt to distinguish lithium-responsive from lithium nonresponsive patients on the basis of sensitivity to lithium inhibition of the epinephrine-induced rise in plasma cyclic AMP is of considerable potential practical importance.
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PMID:Cyclic nucleotides in mental disorder. 625 Mar 53

Adenylate cyclase activity was measured in plasma membranes isolated form Morris Hepatomas (44 and 47C) and from their host livers. We found that the enzyme activity in the tumours was very low, approx. 5% of the level in control and host livers. The amount of cAMP and cGMP in the tumours was also lower than in the host livers but the ratio of cGMP to cAMP in the tumours was increased by a factor of 4-5. The membrane binding capacities for the pancreatic hormones insulin and glucagon were measured. Hepatoma membranes bound less glucagon than those of livers. A decrease in the number of the glucagon receptors was found but there were no changes in the affinity constant. For insulin, we found the same binding capacity as the host and control livers; thus there was an increase in the ratio of insulin bound/glucagon bound in tumours as compared to controls. The plasma levels of insulin in the tumour bearing animals were approximately half of those in control, whereas the glucagon levels in plasma were 60-62% higher in tumour bearing animals. These results are discussed in terms of the characterization of normal, foetal and regenerating liver, in comparison with slow growing hepatomas. The levels of cAMP and cGMP are discussed with respect to control mechanisms of cell proliferation.
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PMID:Some enzyme and hormonal attributes of hepatoma cell membranes. 625 69

In the process of immunization of rabbits with cyclic AMP or cyclic GMP, the plasma concentration of cyclic AMP or cyclic GMP was markedly elevated as the titer of the antiserum increased. The i.v. injection of anti-cyclic AMP or anti-cyclic GMP antiserum into rats or mice also caused a marked increase in the respective cyclic nucleotide in plasma. On the other hand, an injection with the antiserum did not cause any significant increase in urinary cyclic nucleotides. Therefore, the effect of the antiserum seems to be different from that of glucagon or carbamylcholine which increases cyclic AMP or cyclic GMP respectively in both plasma and urine. The injection of the antiserum, but not nephrectomy, caused a significant increase in plasma cyclic nucleotides in adrenalectomized rats. This made it unlikely that the antiserum-induced increase was due to the inhibition of urinary excretion. The plasma cyclic nucleotides, increased by an i.v. injection with the antiserum, servived enzymatic hydrolysis by phosphodiesterase in vitro; most of them proved to be bound to the antibody. It was concluded that the increases in plasma cyclic nucleotides in the process of cyclic nucleotide-immunization were mainly due to decreased metabolic clearance of plasma cyclic nucleotides.
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PMID:Changes in the concentration of cyclic nucleotides dependent on their antibodies in plasma. 625 16

The relationship between cAMP and relaxation was studied in the isolated rat heart beating at constant rate and perfused at constant coronary flow. After treatment during 1 min with different positive inotropic interventions, cyclic nucleotide levels (cAMP and cGMP) and cAMP-dependent protein kinase activity were determined in heart homogenates. Glucagon, norepinephrine, and isoproterenol increased cAMP from 0.503 +/- 0.025 pmol/mg wet wt to 1.051 +/- 0.099, 0.900 +/- 0.064, and 0.982 +/- 0.138, respectively. Simultaneously glucagon, norepinephrine, and isoproterenol increased cAMP-dependent protein kinase activity ratio from 0.21 +/- 0.02 to 0.45 +/- 0.04, 0.33 +/- 0.02, and 0.34 +/- 0.02, respectively. The ratio between maximal velocities of contraction and relaxation (+T/-T) was significantly decreased by these interventions, whereas time to peak tension (TTP) was shortened by norepinephrine and isoproterenol. High calcium, ouabain, and paired stimulation did not affect cAMP levels, TTP, or +T/-T. A striking correlation was found between cAMP-dependent protein kinase activity and relaxation induces, i.e., TTP, -T, or +T/-T (r = +/- 0.7 to -0.9). Results suggest that inotropic interventions increasing cAMP levels might be primarily affecting intracellular mechanisms causing relaxation.
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PMID:Relaxing effect of pharmacologic interventions increasing cAMP in rat heart. 626 90

Although numerous studies have suggested that depression may be associated with a reduction in synaptic noradrenaline in the brain, direct beta-adrenergic receptor agonists have not been tested in the treatment of depression until recently. Moreover, newer theories of antidepressant action suggest that a reduction in beta-adrenergic receptor sensitivity is a better correlate of antidepressant treatment than noradrenaline turnover changes. It is possible to evaluate the beta-adrenergic receptor-adenylate cyclase complex in the human periphery by measuring the plasma cyclic AMP rise after adrenergic agonists. A clinical trial of the beta-2 adrenergic agonist salbutamol in depression provided an opportunity to test whether adrenergic receptor subsensitivity does occur during clinical antidepressant treatment. Plasma cyclic AMP before treatment with salbutamol rose 26% in response to salbutamol 0.25 mg iv. After 1 and 3 weeks of oral salbutamol treatment, depression scores declined significantly in 11 depressed patients, while the plasma cyclic AMP response to iv salbutamol declined over 60%. The beta-adrenergic adenylate cyclase remained subsensitive 4 days after cessation of salbutamol therapy. The results support the concept that receptor sensitivity changes occur during human antidepressant therapy. Data are presented that Li, too, markedly reduces activity of beta-adrenergic adenylate cyclase in humans. The effect was evaluated by studying the effect of Li at therapeutic serum concentrations on the plasma cyclic AMP response to subcutaneous epinephrine. The Li effect is specific, since the plasma cyclic AMP response to glucagon is not inhibited. The plasma cyclic GMP response to subcutaneous epinephrine, suggested as a model for presynaptic alpha-noradrenergic mechanisms, is also partially inhibited by Li therapy. Since cyclic AMP and cyclic GMP may be viewed as balancing substances, their interaction may provide a mechanism for Li's dual clinical effects in mania and depression. It is important that in vivo techniques be developed for evaluating receptor changes. The plasma cyclic AMP response to adrenergic stimulation provides an in vivo measure of receptor function that can be useful in studying drug effects during the clinical treatment of humans.
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PMID:Receptors, adenylate cyclase, depression, and lithium. 626 45

To determine if cGMP might function as a second messenger for insulin, an in situ liver perfusion system was established in which hepatic effects of insulin could be correlated with changes in cyclic nucleotides. Several combinations of insulin (10 mU/ml) and glucose (50 mg/ml) were infused (0.1 ml/min) for 30 min into fasted normal and diabetic rats with removal of a similar volume of blood. Samples of livers were removed at the beginning and end and at various times during the perfusion. In normal animals perfused with buffer alone, hepatic glycogen content fell. When glucose (with or without added insulin) was added to the perfusate, glycogen levels rose. With buffer alone, there was no change in the independent (I) form of glycogen synthase at 10 min but a modest increase at 30 min. With insulin and/or glucose, there as a large increase in the I-form of the enzyme at 10 min and a further rise at 30 min. Neither cGMP nor cAMP changed even though tissue samples were obtained at multiple times throughout the perfusion. Cyclic nucleotides were also measured in liver slices exposed to insulin (1 mU/ml) after 30 min of pre-incubation for stabilization. Although significant increases in cGMP were noted in the tissue exposed to insulin, similar significant rises also occurred in appropriately paired control slices. When glucagon was used in both the in situ perfusion and the paired liver slice systems, the expected rapid and large increases in cAMP levels occurred attesting to the validity of both approaches in evaluating hepatic cyclic nucleotide responses. These results plus the paucity of convincing data in the literature strongly suggest that cGMP can no longer be considered a candidate for the putative second messenger of insulin.
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PMID:Hepatic effects of glucose and insulin independent of cyclic nucleotide changes. 627 20

After 1 min of treatment with different positive inotropic interventions, cyclic nucleotide levels (cAMP and cGMP) and cAMP-dependent protein kinase activity were determined in heart homogenates. Glucagon, norepinephrine, and isoproterenol increased cAMP from 0.503 +/- 0.025 pmol/mg wet weight to 1.051 +/- 0.099, 0.900 +/- 0.064, and 0.982 +/- 0.138, respectively. Simultaneously, cAMP-dependent protein kinase activity ratio rose from 0.21 +/- 0.02 to 0.45 +/- 0.04 with glucagon, 0.33 +/- 0.02 with norepinephrine, and 0.34 +/- 0.02 with isoproterenol. The ratio between maximal velocities of contraction and relaxation (+T/-T) was significantly decreased by these interventions, whereas time to peak tension (TTP) was shortened by norepinephrine and isoproterenol. High calcium, ouabain, and paired stimulation did not affect cAMP-dependent protein kinase activity and +T/-T. Our results suggest that inotropic interventions increasing cAMP levels might primarily affect intracellular mechanisms causing relaxation.
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PMID:Relaxant effect of pharmacological interventions increasing heart cyclic AMP and its protein kinase. 630 90

Control of lipogenesis by glucagon and cyclic nucleotide derivatives was examined in freshly isolated hepatocytes. [14C]Acetate was incorporated at a linear rate for 2 h into cellular lipids and for at least 6 h into medium lipids. About 80% of the incorporated label was recovered in fatty acids. Incorporation of [1-14C]acetate and 3H2O into cellular and medium lipids was inhibited by glucagon (K50 = 8 X 10(-10) M), dibutyryladenosine 3':5'-cyclic monophosphate (K50 = 7.5 X 10(-8) M), and guanosine 3':5'-cyclic monophosphate and its dibutyryl and 8-bromo derivatives, each with K50 = 2.9 X 10(-6) M. Glucagon (10 nM) reduced incorporation of [14C]acetate and 3H2O into fatty acid by 73 and 52%, respectively, and into cholesterol by 24 and 10%, respectively. When added together to hepatocytes at submaximally inhibitory concentrations, dibutyryl cAMP and dibutyryl cGMP exerted additive effects. However, maximal inhibitory concentrations of both produced the same effect as the addition of either nucleotide alone. Thus, this preparation of rat hepatocytes responded to physiological concentrations of glucagon and low concentrations of dibutyryl cAMP. Cyclic guanosine derivatives inhibited lipogenesis, but 100 times greater concentration was required when compared with dibutyryl cAMP. Dibutyryl cAMP and dibutyryl cGMP did not act synergistically.
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PMID:Comparison of glucagon, cAMP, and cGMP effects on lipogenesis in hepatocytes. 630 34

Rat hepatocytes rapidly incorporate [32P]Pi into phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]; their monoester phosphate groups approach isotopic equilibrium with the cellular precursor pools within 1 h. Upon stimulation of these prelabelled cells with Ca2+-mobilizing stimuli (V1-vasopressin, angiotensin, alpha 1-adrenergic, ATP) there is a rapid fall in the labelling of PtdIns4P and PtdIns(4,5)P2. Pharmacological studies suggest that each of the four stimuli acts at a different population of receptors. Insulin, glucagon and prolactin do not provoke disappearance of labelled PtdIns4P and PtdIns(4,5)P2. The labelling of PtdIns4P and PtdIns(4,5)P2 in cells stimulated with vasopressin or angiotensin initially declines at a rate of 0.5-1.0% per s, reaches a minimum after 1-2 min and then returns towards the initial value. The dose-response curves for the vasopressin- and angiotensin-stimulated responses lie close to the respective receptor occupation curves, rather than at the lower hormone concentrations needed to evoke activation of glycogen phosphorylase. Disappearance of labelled PtdIns4P and PtdIns(4,5)P2 is not observed when cells are incubated with the ionophore A23187. The hormone-stimulated polyphosphoinositide disappearance is reduced, but not abolished, in Ca2+-depleted cells. These hormonal effects are not modified by 8-bromo cyclic GMP, cycloheximide or delta-hexachlorocyclohexane. The absolute rate of polyphosphoinositide breakdown in stimulated cells is similar to the rate previously reported for the disappearance of phosphatidylinositol [Kirk, Michell & Hems (1981) Biochem. J. 194, 155-165]. It seems likely that these changes in polyphosphoinositide labelling are caused by hormonal activation of the breakdown of PtdIns(4,5)P2 (and may be also PtdIns4P) by the action of a polyphosphoinositide phosphodiesterase. We therefore suggest that the initial response to hormones is breakdown of PtdIns(4,5)P2 (and PtdIns4P?), and that the simultaneous disappearance of phosphatidylinositol might be a result of its consumption for the continuing synthesis of polyphosphoinositides.
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PMID:Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones. 630 53


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