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: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N6,O2'-dibutyrylcyclo-3',5'-AMP injected to intact rats alone or in combination with theophylline increases the activity of guanidine acetate methyltransferase (GAMT) in liver and pancreas. Cyclic 3',5'-AMP and its dibutyryl analog administered immediately or two hours after the suturing of common bile duct (SCBD) stimulate the increase of pancreatic GAMT activity 2-3 fold. Glucagon, injected intraabdominally simultaneously with SCBD and administration of theophylline, dramatically increases the theophylline effect on the GAMT activity. The freezing of rat pancreas pretreated witn secretin, a hormone structurally similar to glucagon, results in a 1.5-2-fold increase of creatine synthesis from S-adenosylmethionine and guanidinacetic acid. An hour after glucagon administration to intact rats the GAMT activity of liver increases 9 times. The effect of glucagon is enhanced by insulin. Cycloheximide inhibits the increase of GAMT activity, induced by glucagon or a combination of glucagon and insulin. Experiments on tissue homogenates demonstrate that 3',5'-AMP in concentrations of 10(-8) --10(-2) M does not affect the GAMT activity or to some extent inhibits the enzyme. The homogenate incubation in a medium containing 10(-5) M epinephrine or 10(-7) M caffeine and 5 mM Mg2+ leads to an increase in the GAMT activity. Oligomycin removes the stimulating effects of caffeine and Mg2+ on the enzyme activation. This is probably due to the presence of 3',5'-AMP-dependent protein kinase in the mechanism of GAMT activation by cyclic AMP.
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PMID:[The stimulating effect of cyclic AMP, glucagon and insulin on guanidine acetate-N-methyltransferase activity in rat liver and pancreas]. 17 11

Acinar cells from guinea pig pancreas possess two distinct protein kinase activities. Cyclic GMP-dependent kinase elutes as a single peak on diethylaminoethyl (DEAE)- cellulose chromatography, is not inhibited by protein kinase inhibitor, and has a greater affinity for cyclic GMP (half-maximal activation at 20 nM) than for cyclic AMP (half-maximal activation at 100 nM). Cyclic AMP-dependent kinase elutes as two peaks on DEAE-cellulose chromatography, is inhibited by protein kinase inhibitor, and has a greater affinity for cyclic AMP (half-maximal activation at 20 nM) than for cyclic GMP (half-maximal activation at 7 micrometer). Binding of cyclic 3H-nucleotides to the enzyme preparation was rapid, specific, temperature-dependent, and reversible, and there was a close correlation between the ability of a particular cyclic nucleotide to inhibit binding of cyclic 3H-nucleotide and its ability of a particular cyclic nucleotide to inhibit binding of cyclic H-nucleotide and its ability to activate protein kinase. Binding of cyclic 3H--nucleotide could not be described as a simple bimolecular reaction and native cyclic nucleotides accelerated the dissociation of bound, labeled cyclic nucleotide. Vasoactive intestinal peptide or secretin, each of which increases cellular cyclic AMP, caused endogenous activation of protein kinase and inhibition of cyclic [3H]AMP binding but did not alter bindings of cyclic [3H]GMP or cyclic [3H]AMP.
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PMID:Cyclic nucleotide-dependent protein kinase activity in acinar cells from guinea pig pancreas. 21 41

When primary cultured bovine adrenocortical cells were treated with substance P (SP) at concentrations higher than 10 pM, cortisol output increased in a dose-dependent fashion. Although other neurokinins, such as neurokinin A (NKA) and neurokinin B (NKB), were also effective in secreting cortisol, SP was the most potent among the tested neurokinins, the potency order being SP greater than NKA much greater than NKB. This suggests that the NK-1 type receptor on adrenocortical cells may be the site of action of SP on cortisol secretion. The maximal response in SP-induced cortisol secretion was comparable to that elicited by adrenocorticotropic hormone (ACTH). SP-induced cortisol secretion was dependent upon extracellular Ca2+ concentrations, and 45Ca2+ uptake into adrenocortical cells treated with SP was long-lasting. While, in the case of ACTH, 45Ca2+ uptake proceeded transiently, the increase in intracellular cAMP content was much greater compared with that of SP. Although KT-5720, an inhibitor of protein kinase A, inhibited potently ACTH-induced cortisol secretion, SP-induced secretin was not affected by this inhibitor at all. On the other hand, calmodulin inhibitors, such as calmidazolium, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, were not more effective in inhibiting SP-induced cortisol secretion than secretion induced by ACTH. The present study indicates that SP may be one of the physiological stimulants of cortisol secretion and that an increase in intracellular Ca2+ concentration and the subsequent activation of calmodulin may precede SP-induced cortisol secretion.
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PMID:Cortisol secretion induced by substance P from bovine adrenocortical cells and its inhibition by calmodulin inhibitors. 137 83

Using the patch-clamp technique we have identified a Ca2(+)-sensitive, voltage-dependent, maxi-K+ channel on the basolateral surface of rat pancreatic duct cells. The channel had a conductance of approximately 200 pS in excised patches bathed in symmetrical 150 mM K+, and was blocked by 1 mM Ba2+. Channel open-state probability (Po) on unstimulated cells was very low, but was markedly increased by exposing the cells to secretin, dibutyryl cyclic AMP, forskolin or isobutylmethylxanthine. Stimulation also shifted the Po/voltage relationship towards hyperpolarizing potentials, but channel conductance was unchanged. If patches were excised from stimulated cells into the inside-out configuration, Po remained high, and was not markedly reduced by lowering bath (cytoplasmic) Ca2+ concentration from 2 mM to 0.1 microM. However, activated channels were still blocked by 1 mM Ba2+. Channel Po was also increased by exposing the cytoplasmic face of excised patches to the purified catalytic subunit of cyclic AMP-dependent protein kinase. We conclude that cyclic AMP-dependent phosphorylation can activate maxi-K+ channels on pancreatic duct cells via a stable modification of the channel protein itself, or a closely associated regulatory subunit, and that phosphorylation alters the responsiveness of the channels to Ca2+. Physiologically, these K+ channels may contribute to the basolateral K+ conductance of the duct cell and, by providing a pathway for current flow across the basolateral membrane, play an important role in pancreatic bicarbonate secretion.
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PMID:Regulation of maxi-K+ channels on pancreatic duct cells by cyclic AMP-dependent phosphorylation. 169 85

The effect of cholecystokinin (CCK)-gastrin family peptides (caerulein, unsulfated gastrin-17, and pentagastrin) and secretin in activating amiloride-sensitive 22Na uptake were investigated in guinea pig pancreatic acini. Secretin had no effect, but CCK-gastrin peptides stimulated the amiloride-sensitive 22Na uptake. The effect of caerulein was inhibited by dibutyryl guanosine 3',5'-cyclic monophosphate (cGMP) and asperlicin, indicating that activation of the Na+-H+ antiport caused by caerulein is mediated by CCK receptors. The effect of gastrin was dibutyryl cGMP and asperlicin insensitive, whereas the effect of pentagastrin was inhibited by the CCK antagonists but with a low affinity, indicating that the effect of gastrin and that of pentagastrin was CCK receptor independent. The calcium ionophore A23187 caused an increase in amiloride-sensitive 22Na uptake. However, the effect of caerulein, which increased internal calcium concentration, was not modified after depletion of intracellular calcium, and that of CCK-gastrin family peptides was not dependent on external calcium concentration. Activation of amiloride-sensitive 22Na uptake was also induced by 12-O-tetradecanoylphorbol 13-acetate and 1-oleoyl-2-acetyl-glycerol. Activation of protein kinase c may be involved in the mechanism of caerulein or gastrin in activating the Na+-H+ exchange.
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PMID:Distinct activation of Na+-H+ exchange by gastrin and CCK peptide in acini from guinea pig. 244 99

Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is subject to regulation by the cAMP as well as the calcium and cGMP second messenger systems. Treatment of intact rat PC12 cells with neuropeptides including secretin and vasoactive intestinal polypeptide (VIP) stimulated tyrosine hydroxylase activity 2 to 3-fold in vitro. Secretin (EC50 = 10 nM) was about 3 orders of magnitude more potent than VIP (EC50 = 3 microM). A combination of several protease inhibitors failed to enhance the potency of either peptide. Other members of the secretin family including glucagon and peptide histidine isoleucine (PHI) stimulated tyrosine hydroxylase activity to a lesser extent. Somatostatin, which is not homologous to secretin, was ineffective. The maximal response of tyrosine hydroxylase activation to 1 microM secretin occurred within 6-15 sec. Secretin, VIP, and forskolin also enhanced tyrosine hydroxylase activity (3,4-dihydroxyphenylalanine production) in intact cells, as determined by high performance liquid chromatography and electrochemical detection. Secretin, VIP, PHI, and glucagon increased the levels of cAMP in PC12 cells more than 10-fold, as determined by radioimmunoassay. We also demonstrated that cAMP is released from the cells into the incubation medium following secretin treatment. Secretin and VIP treatment also enhanced the activity of cAMP-dependent protein kinase in a concentration-dependent fashion, as measured subsequently in vitro. Based on the greater potency of secretin in comparison with VIP, PHI, and glucagon, we suggest that the PC12 cells contain a secretin-preferring receptor that increases cAMP levels and brings about an activation of tyrosine hydroxylase activity through the stimulation of cAMP-dependent protein kinase.
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PMID:Regulation of tyrosine hydroxylase activity in rat PC12 cells by neuropeptides of the secretin family. 257 21

Figure 4 summarizes the steps by which Ca2+ and cyclic AMP-mediated secretagogues activate enzyme secretion in the pancreatic acinar cell. CCK and acetylcholine bind to specific plasma membrane receptors and through an as yet incompletely understood mechanism give rise to an elevation in free cytoplasmic Ca2+. A question central to this scheme is whether receptor binding leads to intracellular Ca2+ mobilization through generation of a diffusable mediator. Clues to answering this question may come from a) determining whether Ca2+ is released from the plasma membrane in addition to one or more intracellular organelles, and b) examining the role (if any) of membrane phosphatidylinositol metabolism in Ca2+ mobilization. A second class of secretagogues, represented by VIP and secretin, bind to their specific receptors and cause the accumulation of cyclic AMP. Cyclic AMP potentiates Ca2+ in activating secretion, and in some species, cyclic AMP may activate secretion independently of Ca2+. Ca2+ may act by regulating the activity of calmodulin dependent protein kinase(s) and phosphatase(s) and a phospholipid dependent kinase (protein kinase C) which has also been shown to be activated by diacylglycerol; cyclic AMP activates a distinct kinase termed protein kinase A. These kinases and phosphatases then alter the phosphorylation of specific proteins which are presumed to play structural or regulatory roles in exocytosis. Potentiation may thus result from interaction of Ca2+ and cyclic AMP at the level of a protein kinase, phosphatase or protein substrate.
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PMID:Stimulus-secretion coupling in pancreatic acinar cells. 609 80

Histamine, vasoactive intestinal polypeptide (VIP), secretin and prostaglandin E2 (PGE2) stimulate cyclic AMP-dependent protein kinase activity in gastric glands isolated from the guinea pig fundus and antrum. The effects are observed in the absence of any cyclic AMP phosphodiesterase inhibitor and maximal stimulation of the protein kinases occurs within 0.5 min of incubation at 20 degrees C. As shown by dose-response studies, VIP is equally potent in the antrum as in the fundus (identical values of the activation constant are found in both types of gland, Ka = 2.5 . 10(-9) M); a similar situation occurs for PGE2 action (but with Ka = 2.0 . 10(-8) M), whereas the potency of histamine is higher in the fundus (ka = 8.0 . 10(-6)M) than in the antrum (Ka = 5.0 . 10(-5) M). Secretin also increases the protein kinase activity ratio but with a 1000 times lower potency than VIP. In fundic glands, histamine (10(-3) M) is the activator of by far the greatest efficacy (increasing protein kinase activity at 4 times of the basal value) as compared with the effect obtained with 10(-6) M PGE2 (2.7 times) and 10(-7) M VIP (1.4 times). In contrast, VIP has greater efficacy (2.3 times) than histamine (2.1 times) in antral glands, whereas PGE2 is equally active in the two parts of the gastric mucosa. In addition, somatostatin (10(-6) M) inhibits partially (30%) and specifically the protein kinase activation stimulated by histamine, whereas it has no effect on VIP- and PGE2-induced activation. The results are consistent with increased cyclic AMP levels in response to these effectors in this system. A physiological role of histamine on acid-secreting parietal cells, of VIP on nonparietal cells and of PGE2 on both cell types, mediated by the cyclic AMP/protein kinase system is proposed.
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PMID:Differential effects of histamine, vasoactive intestinal polypeptide, prostaglandin E2 and somatostatin on cyclic AMP-dependent protein kinase activation in gastric glands isolated from the guinea pig fundus and antrum. 612 56

Rabbit isolated gastric glands were used to investigate the dependence of pepsinogen and acid secretions on extraglandular pH. Changing pH from 8.0 to 6.7 caused small increases in pepsinogen secretory responses to isoproterenol, carbachol, cholecystokinin octapeptide, Boots' secretin, and hyperosmolarity but caused large increases in responses to 8-bromoadenosine 3',5'-cyclic monophosphate (8BrcAMP), 8-bromoinosine 3',5'-cyclic monophosphate (8BrcIMP), and forskolin. The similar effect of pH on responses to 8BrcAMP, 8BrcIMP, and forskolin was suggested to reflect a commonality in their proposed mechanisms of action. It was concluded that reducing extraglandular pH indirectly caused an increase in activity of cAMP-dependent protein kinase or of a subsequent step in cAMP-dependent regulation of pepsinogen secretion. 8BrcAMP-stimulated acid secretion also increased as pH was changed from 8.0 to 6.7, and a similar explanation of the effect was suggested. However, histamine-stimulated acid secretion and adenyl cyclase activity decreased markedly as pH was lowered over this range. It was suggested that cAMP was rate limiting for stimulation by histamine and that the effect of pH on histamine-stimulated acid secretion could be attributed to an effect of pH on adenyl cyclase activity.
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PMID:pH dependence of pepsinogen and acid secretion in isolated gastric glands. 619 90

Vasoactive intestinal peptide stimulated cyclic AMP-dependent protein kinase activity in human blood mononuclear cells. The simultaneous presence of a phosphodiesterase inhibitor was required to elicit maximal activation. The apparent Ka value of half the maximal stimulation was about 60 pmol. Secretin exhibited a 170-times lower potency. Other peptides such as glucagon or insulin had no effect even at 1 microM.
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PMID:Activation of cyclic AMP-dependent protein kinase by VIP in blood mononuclear cells. 620 83


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