Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isoprenaline produced a dose-dependent decrease in the activity of an endogenous, specific inhibitor of cAMP-dependent protein kinase (type I inhibitor) in rat hippocampus, brain stem and pineal gland. Prolonged, 21-days treatment with some antidepressant (imipramine, nomifensin and mianserin) markedly reduced the response of the type I inhibitor activity to isoprenaline. To obtain the significant decrease of the type I inhibitor activity, five times higher dose of isoprenaline had to be used in these animals than in control rats. Mianserin is known to produce a decrease of the activity of adenylate cyclase coupled to beta-adrenergic receptors without changing the number of receptor binding sites. In the present study we have shown that also mianserin after prolonged treatment produces subsensitivity of beta-adrenergic receptors when measured by the response of the type I inhibitor activity to isoprenaline. Single doses of imipramine, nomifensin and mianserin did not change the isoprenaline-induced decrease of the type I inhibitor activity. It seems that the isoprenaline-induced decreased of the type I inhibitor activity can be used as an index of beta-adrenergic receptor reactivity.
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PMID:Isoprenaline-induced changes in type I inhibitor activity as an index of beta-adrenergic receptor subsensitivity. 608 61

Isolated guinea pig hearts were used to determine whether an extracellular (interstitial) or intracellular pool of myocardial adenosine is most important in attenuating the catecholamine-induced enhancement of cardiac contractile state and glycogenolysis. Isoproterenol (2 X 10(-8) M) stimulation of hypoxic (30% O2) perfused hearts produced a marked elevation in tissue and effluent perfusate adenosine levels that were greater than the increases observed with the isoproterenol stimulation of oxygenated hearts (95% O2). In the isoproterenol stimulated hypoxic hearts nitrobenzylthioinosine (NBMPR), a potent inhibitor of adenosine cellular transport, further increased tissue adenosine content and markedly decreased the perfusate level of the nucleoside. Assuming that perfusate levels of adenosine correlate directly with extracellular levels, NBMPR was used as a tool to increase the intracellular and decrease the extracellular content of the nucleoside. When compared to responses in oxygenated hearts, hypoxia reduced the isoproterenol-produced increase in myocardial cyclic AMP content, cyclic AMP-dependent protein kinase activity and contractility but enhanced the increase in glycogen phosphorylase alpha formation. NBMPR completely prevented the reduction of the isoproterenol-induced cyclic AMP and cyclic AMP-dependent protein kinase responses but only partially prevented the attenuation of the contractile response. The increase in phosphorylase alpha formation in the hypoxic isoproterenol stimulated hearts was not influenced by NBMPR. The results suggest that an increase in extracellular adenosine is more influential than an elevation of intracellular adenosine in attenuating beta-adrenoceptor-elicited increases in myocardial cyclic AMP content, cyclic AMP-dependent protein kinase activity and contractile state.
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PMID:Role of extracellular and intracellular adenosine in the attenuation of catecholamine evoked responses in guinea pig heart. 609 51

Isoprenaline and adrenaline produced an increase of cAMP content and a decrease of the activity of the endogenous inhibitor of cAMP-dependent protein kinase (type I inhibitor) in human lymphocytes and in rat heart. The maximal effect was seen at a concentration of 10(-6) M. Noradrenaline and dopamine required much higher concentration to elicite the same effect. The decrease of type I inhibitor activity was mediated through beta-adrenergic receptors because propranolol, but not phentolamine, blocked the effects produced by isoprenaline. Stimulation of beta-adrenergic receptors did not influence the activity of type II inhibitor.
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PMID:The effect of beta-receptor stimulation on the activity of the inhibitor of cAMP-dependent protein kinase. 612 59

From a homogenate of rabbit colon a crude protein kinase was isolated. The phosphorylation of histone by this enzyme was maximal at 20 mM NaF. Higher concentrations inhibited the incorporation of 32P. After chromatography on a DEAE-cellulose column the crude protein kinase was partly purified. Cyclic AMP and cGMP stimulated the protein kinases eluted at 0.09 M-NaCl (Type I) and at approximately 0.2M-NaCl (Type II). The main peak was of type II. Mix (1-methyl-3-isobutylxanthine) relaxed the rabbit colon muscle. The increase in the protein kinase activity was closely correlated to the changes of the cAMP level. The cGMP content was also increased. Isoprenaline increased the cAMP level and the protein kinase activity of the colon muscle. Isoprenaline had no effect on the cGMP level. It is suggested that relaxing drugs which increase the cAMP level of rabbit colon muscle may activate protein kinase. This enzyme might be an important factor of the cAMP mediated relaxing mechanism.
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PMID:Effects of isoprenaline and 1-methyl-3-isobutylxanthine on cyclic nucleotides and cyclic AMP-dependent protein kinase in rabbit colon smooth muscle. 615 52

Divalent cations and agents elevating cellular cAMP were tested for their effects on parathyroid hormone (PTH) secretion and protein kinase activity in dispersed bovine parathyroid cells. After incubation with secretagogue for 5-30 min, cells were sedimented, PTH in the supernatant was determined by RIA, and the pellet was disrupted by sonication for the measurement of protein kinase activity. Preliminary studies established conditions where the protein kinase activity ratio (AR = activity in the absence divided by that in the presence of 10(-6) M cAMP in the kinase assay) remained stable during the preparation and assay of cellular extracts. (-)Isoproterenol caused a rapid (within 5 min) increase in the AR from 0.28 to 0.63, which returned to 0.25-0.3 within 5 min after the addition of the potent beta-adrenergic blocker (-)propranolol. (-)Isoproterenol, dopamine, and the phosphodiesterase inhibitor methylisobutylxanthine caused parallel, dose-dependent increases in PTH release and the protein kinase AR of 2- to 2.5-fold. Calcium and magnesium, on the other hand, despite causing 2- to 4-fold inhibition of secretion at 2 and 5 mM, respectively, had no effect on the AR. Calcium (2.0 mM) likewise had only a modest (0-25%) inhibitory effect on the isoproterenol-stimulated increase in the AR in spite of a 3- to 4-fold inhibition of agonist-stimulated secretion. These results suggest that the stimulation of secretion associated with agents that elevate cAMP is mediated by cAMP. Changes in the degree of activation of protein kinase, on the other hand, cannot quantitatively for the effects of divalent cations on basal or agonist-stimulated secretion.
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PMID:Adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase and the regulation of parathyroid hormone release by divalent cations and agents elevating cellular cAMP in dispersed bovine parathyroid cells. 617 21

This study compares the effects of forskolin and isoproterenol on lipolysis and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in hamster white adipocytes. Rates of lipolysis in forskolin-stimulated cells were equivalent to those in cells incubated with isoproterenol, but cAMP levels were more than 10-fold greater in the presence of forskolin. The stimulatory effects of forskolin were partially inhibited by N6-phenylisopropyl adenosine but not by 2',5'-dideoxyadenosine. In other experiments, cells were exposed to forskolin in combination with either isoproterenol or adenosine deaminase. A concentration of forskolin that caused only a small increase in lipolysis was used. When isoproterenol or adenosine deaminase were added with forskolin, lipolysis increased dramatically, but cAMP content either did not change, as occurred with isoproterenol, or increased only slightly with adenosine deaminase. Isoproterenol potentiation of forskolin's lipolytic action persisted in the absence of extracellular K+, even though the lipolytic response to isoproterenol alone was absent in K+-free media. These data demonstrate that the lipolytic responses of adipose tissue are more complex than are responses simply in proportion to cellular concentration of cAMP. Such complexity could arise if lipolytic regulatory factors other than cAMP existed or if cAMP and protein kinase were functionally segregated within adipocytes.
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PMID:Stimulation of cAMP accumulation and lipolysis in hamster adipocytes with forskolin. 619 25

Isoproterenol-induced amylase release from rabbit parotid acini was examined in relation to cyclic AMP (cAMP) concentrations, cAMP-dependent protein kinase (cAMP-PK) activity ratios and protein phosphorylation. Initial stimulation of amylase release by isoproterenol was preceded by increases in cAMP, cAMP-PK activity ratios and phosphorylation of a 34,000 MW (major) and a 30,000 MW (minor) protein in the microsomal fraction. When propranolol was added, decreases in cAMP concentrations and cAMP-PK activity ratios preceded the reduction in amylase release. Detailed analysis was performed on the 34,000 MW protein. The relation of dephosphorylation of protein 34 and reduction in amylase release was complex. Slight dephosphorylation occurred before or concurrently with the decrease in amylase release; however, maximal dephosphorylation was preceded by maximal inhibition of amylase release. When secretion of amylase was reinstituted by isoproterenol or forskolin, increases in cAMP and cAMP-PK activity ratios occurred before or in concert with amylase release but rephosphorylation of protein 34 occurred after the start of amylase release. Photoaffinity labeling studies using [32P]-8-azidoadenosine-3',5'-cyclic monophosphate indicated that proteins 34 and 30 were not regulatory subunits of cAMP-PK or their breakdown products. Although these data are consistent with phosphorylation of proteins 34 or 30 being required for triggering initial secretion, maximum dephosphorylation was not essential for inhibition of secretion. Furthermore, initiation of amylase release by the gland after a short period of quiescence did not depend on prior phosphorylation of protein 34. These data may indicate the absence of a requirement of amylase release for phosphorylation of protein 34.
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PMID:Isoproterenol-induced amylase release in rabbit parotid acini: relation of protein phosphorylation, cyclic AMP and related kinase activity to changes in secretory rate. 620 8

The interrelationships among cAMP-dependent protein kinase activity, lipolysis, and cellular concentrations of cAMP were investigated in hamster epididymal adipose tissue. Isoproterenol, norepinephrine, and theophylline increased the protein kinase activity assayed in tissue extracts with no added cAMP, but not in the presence of added cyclic nucleotide. The maximum rate of lipolysis was associated with a nearly three-fold increase in cAMP levels and a protein kinase activity ratio of 0.8 (the ratio of activity assayed without cAMP to that assayed with cAMP). Rates of lipolysis less than maximum were associated with lesser degrees of protein kinase activity and lower levels of cAMP. The relatively pure alpha-adrenergic agent phenylephrine partially suppressed the isoproterenol-stimulated protein kinase activity, lipolysis, and cAMP levels. Conversely, the alpha-adrenergic blocking agent phentolamine increased the activity of protein kinase and cAMP levels in adipose tissues exposed to norepinephrine. These data are consistent with the primary role for cAMP and its dependent protein kinase in control of lipolysis in adipose tissue. Moreover, our data are consistent with the view that the antilipolytic action of alpha-adrenergic agents is mediated by a decrease in activity of protein kinase, caused by a decrease in cellular cAMP concentrations.
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PMID:Activation of adenosine 3',5'-monophosphate-dependent protein kinase and its relationship to cyclic AMP and lipolysis in hamster adipose tissue. 624 85

1. The relaxing action of the beta-adrenergic agent, isoprenaline, on the porcine coronary artery was investigated in relation to the cyclic AMP level, the endogenous binding of cyclic AMP to the regulatory unit of cyclic AMP dependent protein kinase or the phosphorylation as a result of activation of protein kinase of the muscle homogenate in Krebs solution and excess [K]o solution. These relations were also compared with those of the rat cardiac muscle, in which isoprenaline showed a positive inotropic action. 2. Excess [K]o decreased the cyclic AMP level in proportion to the amplitude of K-induced contracture in the porcine coronary artery. Isoprenaline increased the cyclic AMP level in Krebs solution, while it had no effect in excess [K]o. 3. In the porcine coronary artery, the particulate fraction possessed only 5% of the total cyclic AMP dependent protein kinase, while in the rat cardiac muscle, the particulate fraction was 25% of the total protein kinase. 4. The cyclic AMP dependent protein kinase in the particulate fraction of the porcine coronary artery was already saturated with the endogenous cyclic AMP. However, the binding of cyclic AMP to the protein kinase in the particulate fraction in the cardiac muscle and in the cytosol fraction of both tissues were increased in accordance with the cyclic AMP level. In the coronary artery, the protein kinase in the cytosol fraction was bound to a greater extent with cyclic AMP than was measured in the rat cardiac muscle. 5. In the rat cardiac muscle, isoprenaline enhanced the phosphorylation, detected by autoradiography of SDS gel electrophoresis in individual fractions of phosphorylated protein, while little enhancement was observed in the porcine coronary artery. 6. These observations led to the conclusion that in the porcine coronary artery, beta-adrenergic agent increases the levels of cyclic AMP but does not increase the phosphorylation. If the phosphorylation catalysed by cyclic AMP dependent protein kinase was utilized for Ca mobilization in the cell, the change in the cyclic AMP level would probably not have a causal relation to the muscle tone. This conclusion, however, may not be applicable in the case of the cardiac muscle.
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PMID:Does activation of cyclic AMP dependent phosphorylation induced by beta-adrenergic agent control the tone of vascular muscle? 625 32

The rat heart contains a large amount of two protein kinase inhibitors. The type I inhibitor blocks the activity of cAMP-dependent protein kinase while the type II inhibitor blocks cGMP-dependent protein kinase, cAMP-dependent protein kinase and cyclic nucleotide-independent protein kinase. Isoproterenol produced a dose-dependent decrease of the type I inhibitor activity and an increase of cAMP content in rat heart. The decrease of the type I inhibitor activity is mediated through adrenergic beta receptor because propranolol and practolol but not phentolamine prevented the effects of isoproterenol. Moreover, prior treatment with aminophylline markedly enhanced isoproterenol-induced increase of cAMP content and decrease of the type I inhibitor activity. Isoproterenol did not change the activity of the type II inhibitor. These results are compatible with the hypothesis that the neurotransmitter generated cAMP modulates phosphorylation in the heart by changing the relationship between cAMP-dependent protein kinase and the type I inhibitor activity.
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PMID:Modulation of the activity of endogenous protein kinase inhibitors in rat heart by the beta adrenergic receptor. 626 7


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