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 effects of the alpha-adrenergic agonist phenylephrine on the levels of adenosine 3':5'-monophosphate (cAMP) and the activity of the cAMP-dependent protein kinase in isolated rat liver parenchymal cells were studied. Cyclic AMP was very slightly (5 to 13%) increased in cells incubated with phenylephrine at a concentration (10(-5) M) which was maximally effective on glycogenolysis and gluconeogenesis. However, the increase was significant only at 5 min. Cyclic AMP levels with 10(-5) M phenylephrine measured at this time were reduced by the beta-adrenergic antagonist propranolol, but were unaffected by the alpha-blocker phenoxybenzamine, indicating that the elevation was due to weak beta activity of the agonist. When doses of glucagon, epinephrine, and phenylephrine which produced the same stimulation of glycogenolysis or gluconeogenesis were added to the same batches of cells, there were marked rises in cAMP with glucagon, minimal increases with epinephrine, and little or no changes with phenylephrine, indicating that the two catecholamine stimulated these processes largely by mechanisms not involving cAMP accumulation. DEAE-cellulose chromatography of homogenates of liver cells revealed two major peaks of cAMP-dependent protein kinase activity. These eluted at similar salt concentrations as the type I and II isozymes from rat heart. Optimal conditions for preservation of hormone effects on the activity of the enzyme in the cells were determined. High concentrations of phenylephrine (10(-5) M and 10(-4) M) produced a small increase (10 tp 16%) in the activity ratio (-cAMP/+cAMP) of the enzyme. This was abolished by propranolol, but not by phenoxybenzamine, indicating that it was due to weak beta activity of the agonist. The increase in the activity ratio of the kinase with 10(-5) M phenylephrine was much smaller than that produced by a glycogenolytically equivalent dose of glucagon. The changes in protein kinase induced by phenylephrine and the blockers and by glucagon were thus consistent with those in cAMP. Theophylline and 1-methyl-3-isobutylxanthine, which inhibit cAMP phosphodiesterase, potentiated the effects of phenylephrine on glycogenolysis and gluconeogenesis. The potentiations were blocked by phenoxybenzamine, but not by propranolol. Methylisobutylxanthine increased the levels of cAMP and enhanced the activation of protein kinase in cells incubated with phenylephrine. These effects were diminished or abolished by propanolol, but were unaffected by phenoxybenzamine. It is concluded from these data that alpha-adrenergic activation of glycogenolysis and gluconeogenesis in isolated rat liver parenchymal cells occurs by mechanisms not involving an increase in total cellular cAMP or activation of the cAMP-dependent protein kinase. The results also show that phosphodiesterase inhibitors potentiate alpha-adrenergic actions in hepatocytes mainly by a mechanism(s) not involving a rise in cAMP.
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PMID:Studies on the alpha-andrenergic activation of hepatic glucose output. II. Investigation of the roles of adenosine 3':5'-monophosphate and adenosine 3':5'-monophosphate-dependent protein kinase in the actions of phenylephrine in isolated hepatocytes. 0 57

Splenic lobes from the pancreas of newborn rats (48-64) hr. were used for the in vitro investigation of cyclic AMP, glucose and amino acid interaction in hormonal secretion. The slight discrepancy found in glucagon relaease with radioimmunoassay and binding assay to specific receptors in liver does not affect the ratio of stimulated to control values. The insulin release due to gheophylline dibutyrl cyclic AMP (dbcAMP) or to arginine is glucose-dependent as in adult rats and provides an index for the validity of the preparations. Glucose alone is efficient in stimulating insulin release but does not affect glucagon secretion; however simultaneous addition of 10 mM arginine, alanine, and lysine (A.A.) or of arginine alone resulted in a higher glucagon release at 1.6 mM than at 16.7 mM GLUCOSE. Theophylline (5 mM)and dbcAMP (2mM) induced a 2=fold increase in glucagon release at low or hight glucose concentrations . Incubation of theophylline (10 mM) and A.A. or arginine resulted in a considerable increase in glucagon release. Potentation of the 3 A.A.-induced glucagon reby dbcAMP was about 1800% no matter what the glucose concentration; similar observations were made for insulin with a 700% potentiation of the 3 A.A.effect glucagon was released more effectively by dbcAMP than was insulin,whereas the reverse was observed with theophylline. These findings suggest that knowledge of the cyclic AMP content is essential when assessing the influence of substrates on glucagon release. The combination of substrates with cyclic AMP clearly demonstrated that potentiation of glucagon release occurs mainly with amino acids, whereas for insulin occurs mainly with amino acids, whereas for insulin release it is mainly glucose which potentiates release.
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PMID:Interaction of amino acids and cyclic AMP on the release of insulin and glucagon by newborn rat pancreas. 16 77

An injection of cortisone acetate at a dose of 5 mg/100 g body weight concomitant with dibutyryl cyclic AMP prevents the increase in the activity of rat liver cytosol serine aminotransferase (L-serine:pyruvate aminotransferase, EC 2.6.1.51) elicited by the nucleotide with a lag of about 2 h. If the glucocorticoid is given 2 h prior to the nucleotide inducer, the lag disappears. The inhibitory effect of cortisone acetate gradually decays and is no longer detectable 12 h following its administration. Theophylline, insulin and glucose at doses which affect significantly the level of tyrosine aminotransferase, have not effect on the level of serine aminotransferase and on the cortisone inhibition. The inhibitory effect of the glucocorticoid on the dibutyryl cyclic AMP-mediated increase in serin aminotransferase diminishes with the age of animall. Increases in the enzyme activity by a single dose of glucagon can also be inhibited by cortisone acetate and actinomycin D as in the case with dibutyryl cyclic AMP as an inducer. The possibility of the existence of a specific inhibitory factor which is formed in response to cortisone acetate is discussed.
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PMID:Inhibitory effect of cortisone acetate on the stimulation of rat liver cytosol L-serrine. Pyruvate aminotransferase by dibutyryl adenosine 3,5-monophosphate. 16 60

Activation of adrenergic beta receptors has been found to stimulate insulin release in vitro that may be mediated through the augmentation of cyclic AMP in the beta cell. The activation of adrenergic alpha receptors in the beta cell inhibits the insulin release. The present studies have shown that isoproterenol (0.62 mug/ml) and sodium dibutyryl cyclic AMP (50 mug/ml) stimulate the insulin secretion and inhibit the glucagon secretion in the presence of 50 mg/100 ml glucose by the isolated pancreatic perfusion of the rat, while norepinephrine (0.5 mug/ml) inhibits the insulin secretion induced by 150 mg/100 ml glucose and stimulates the glucaton secretion. Theophylline (50 mug/ml) does not stimulate the insulin and the glucagon secretion. When norepinephrine is added to theophylline, the output of glucagon does not occur. From these results it can be deduced that the pancreatic alpha cell function may be inhibited by elevation of intracellular cyclic AMP, in contrast to the beta cell function which is stimulated by an increment of cyclic AMP.
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PMID:Secretory regulation of endocrine pancreas: Cyclic AMP and glucagon secretion. 16 30

The influence of various agents on calcitonin release from human thyroid was studied in vitro. Under the condition of this investigation, calcium, magnesium and phosphate did not stimulate calcitonin release from short-term incubated slices of human thyroid. However, pentagastrin and USP glucagon were potent stimulators of calcitonin release. Theophylline and dibutyryl cyclic AMP were also potent stimuli. A highly purified preparation of pancreatic glucagon was without an effect. Those agents which stimulated calcitonin release were associated with augmented cyclic AMP accumulation. Although maximal discharge of calcitonin required the presence of calcium, out in vitro experiments raise the question as to whether a gastrointestinal hormone, rather than calcium, might not be the principal agent affecting calcitonin release.
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PMID:In vitro studies of calcitonin release in man. 17 Dec 4

Theophylline, glucagon, and SQ-20009 induce a choleresis in the dog characterized by a proportionate increase in erythritol clearance and bile flow, no increase in bile salt excretion, and by an isosmotic solution of similar electrolyte composition. The increment in bile appears to originate at the canaliculus in response to increased cyclic-AMP.
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PMID:Characteristics common to choleretic increments of bile induced by theophylline, glucagon and SQ-20009 in the dog. 17 39

Plasma concentrations of glucose, alanine, and glucagon were measured after 24 hour fasting in newborn and infant sheep and in response to infusion of alanine alone and concurrently with theophylline. The plasma glucagon response to alanine was minimal in newborn sheep; in contrast, alanine produced a brisk response in plasma glucagon concentration in infant sheep. Glucose concentrations were unchanged in both groups. Theophylline enhanced blood glucagon and glucose responses to alanine in newborn animals but had minimal effects on the response of the infant sheep. These data, considered with earlier data in fetal sheep, suggest a progressive maturation of pancreatic islet alpha-cell glucagon secretion in the sheep during the postnatal period and suggest that the blunted glucagon response observed in the neonate is related to immaturity of the glucagon secretion mechanisms rather than deficient synthesis of the hormone. This immaturity may be related to impaired synthesis and/or enhanced degradation of cyclic adenosine monophosphate (cAMP) or to diminished responsiveness to cAMP.
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PMID:Effects of fasting and theophylline on alanine-stimulated glucagon secretion in neonatal and infant sheep. 17 57

Lipolysis in isolated swine adipocytes was stimulated by epinephrine, dibutyryl cyclic AMP, and weakly by adrenocorticotropin but not by glucagon or cyclic AMP. Theophylline, a phosphodiesterase inhibitor, stimulated lipolysis and greatly enhanced the activity of adrenocorticotropin. The epinephrine-stimulated lipolytic activity, expressed on a tissue or cell volume basis, was greatest at 25 days postpartum, whereas, expressed on a cell basis, the activity was maximal at day 80. Regardless of the mode of expression, the activity at day 150 was low. Cells from younger animals were more sensitive to epinephrine than cells from older animals.
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PMID:Lipolytic activity of swine adipocytes. 17 32

The effect of glucagon, Vasoactive Intestinal Polypeptide (VIP), secretin and gut glucagon on the cyclic adenosine 3'5' monophosphate (cAMP) level, and on the specific binding of these 125I-peptides to the adipocyte plasma membrane was measured in chicken adipocytes and compared to the results obtained in rat adipocytes. The displacement of 125I-glucagon from its specific sites was observed with about the same concentration of unlabeled hormone in fat cell plasma membranes of both species. However, the rise in cAMP induced by glucagon was much higher in chicken than in rat adipocytes. In chicken fat cells unlike rat fat cells, the cAMP accumulation elicited by glucagon was maintained during at least 60 min even in the absence of theophylline. Theophylline at 1-10 mM potentiated the glucagon-stimulated cAMP levels in rat fat cells, but had only a slight effect, if any, in chicken adiposyces. Porcine VIP, secretin or gut glucagon exerted no detectable action on the cAMP level of chicken adipocytes. The lack of cAMP accumulation was in good agreement with the absence of binding of 125I-VIP and 125I-secretin by chicken plasma membranes. These findings suggest that: 1) the difference of glucagon effect in rat and chicken fat cells results from variations in the rate of degradation of cAMP rather than from differences in the specific binding of glucagon between the two species; 2) the use of chicken fat cells is suitable to discriminate between glucagon and structurally related peptides from mammals.
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PMID:Interactions of glucagon and related peptides with chicken adipose tissue. 18 29

The effects of carbamylcholine (Cch), the divalent cation ionophore A23187 and Ca2+ on the cyclic 3',5'-guanosine monophosphate (cGMP) and cyclic 3',5'-adenosine monophosphate (cAMP) content of rat renal cortical slices were examined. In both the presence and absence of 10 mM theophylline, Cch detectably increased cGMP within 15 sec, with peak responses noted by 2 min. The maximal cGMP response to Cch alone (0.05 mM) was an increase of two- to three-fold over control. Theophylline, which was routinely present in the incubations and which alone increased cGMP of the slices two-fold over basal during 20 min incubations, potentiated the response to Cch (maximal increase, five- to sixfold over theophylline alone). The action of Cch to increase renal cortical cGMP was blocked by prior addition of atropine and was dependent upon the presence of Ca2+ in the incubation media. Exclusion of Ca2+ lowered basal cGMP and abolished increases mediated by Cch, while exclusion of Mg2+ was without detectable effect on cGMP. In slices incubated initially without Ca2+, reexposure to Ca2+ for 1min partially restored the cGMP response to Cch, and reexposure for 3 min completely restored this response. Since prior incubation of tissue in Ca2+-free buffer for only 2 min was sufficient to block the cGMP responses to Cch, depletion of tissue Ca2+ did not appear to be involved. A23187 also increased renal cortical cGMP fivefold in the presence of Ca2+. Its effects were not additive with those of Cch and were not additive with those of Cch and were not expressed by Mg2+ in Ca2+-free media. By contrast, tetracaine, which blocks Ca2+ transport across or binding to biologic membranes, reduced basal cGMP and inhibited the actions of Cch and A23187 to increase cGMP in cortical slices incubated with Ca2+. The action of 1 mM tetracaine to block Cch-mediated increases in cGMP was partially reversed by increasing media Ca2+ from 1.5 to 5 mM, but not by increasing media Mg2+ to 5 mM. In contrast to their effects on cGMP, Cch, A23187, Ca2+ exclusion, and tetracaine did not detectably alter basal renal cortical cAMP or cAMP responses to parathyroid hormone (PTH). Conversely, concentrations of PTH, glucagon, and isoproterenol which maximally increased renal cortical cAMP did not alter cGMP. Furthermore, prior incubation of slices with Cch did not alter their subsequent cAMP response to PTH at a time when cGMP levels were still elevated, while prior incubation with PTH did not affect the subsequent cGMP response to Cch at a time when cAMP was increased. These studies demonstrate modulation of renal cortical cGMP by cholinergic stimuli and Ca2+. They also indicate that cGMP and cAMP in renal cortex can be regulated independently.
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PMID:Calcium-dependent regulation of guanosine 3',5'-monophosphate in renal cortex: effects of ionophore A23187 and tetracaine and evidence for independent control of adenosine 3',5'-monophosphate. 18 65


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