Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TLCK (N-alpha-tosyl-L-lysine chloromethyl ketone) inhibits protein kinase C whether or not the enzyme is under the regulation of Ca2+ and phospholipid. TLCK (IC50 = 1 mM) is a much more potent inhibitor of protein kinase C than TPCK (N-alpha-tosyl-L-phenylalanine chloromethyl ketone) (IC50 = 8 mM), suggesting that the lysyl moiety of TLCK may be specifically recognized by the active site of protein kinase C. These results extend the evidence that the active site of protein kinase C recognizes basic amino acids, and suggest that the active sites of protein kinase C and the cAMP-dependent protein kinase, which is also inhibited by TLCK and TPCK, are structurally related.
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PMID:N-alpha-Tosyl-L-lysine chloromethyl ketone and N-alpha-tosyl-L-phenylalanine chloromethyl ketone inhibit protein kinase C. 404 11

The effects of estrogens 17beta-estradiol (17beta-E2), 17alpha-estradiol (17alpha-E2) and diethylstilbestrol (DES) on CaCl2 (3mM)-induced contractions on rat aorta strips have been assayed. Both 17alpha-E2 and DES, but not the 17beta-E2 relaxed and inhibited the contraction induced by CaCl2. The antiestrogen tamoxifen (0.1, 1 and 3 microM) antagonizes, in a concentration-dependent way, the relaxant effect of 17alpha-E2 but the relaxation induced by DES is only significantly antagonized with 3 microM of tamoxifen. Cycloheximide (0.1 and 0.3 mM) does not modify the 17alpha-E2 or DES effects. However, the inhibitors of cAMP-dependent protein kinase TPCK (1 microM) and Rp-cAMPS (10 microM) inhibit the relaxation induced by 17alpha-E2 and DES. The elimination of endothelium by rubbing, significantly inhibits the effect of DES but does not modify the effect of 17alpha-E2. Our results suggest that estrogen-induced relaxation is a non-genomic effect possibly or presumably produced by activation of estrogenic receptors and mediated by cAMP. The DES-effect is partially endothelium-dependent but the effect of 17alpha-E2 is independent of endothelium.
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PMID:Mechanisms involved in the relaxant effect of estrogens on rat aorta strips. 863 14

1. The effect of zeranol (3-100 microM) on rat uterus contractions induced by KCl (60 mM) and CaCl2 (30 microM-10 mM) has been assayed. 2. Zeranol relaxed the tonic contraction induced by KCl in a concentration-dependent manner (IC50 15.62 +/- 2.66 microM). CaCl2 (0.1-10 mM) did not counteract the relaxing effect of zeranol. 3. CaCl2 (30 microM -10 mM) produced a concentration-dependent contraction of rauuterus in medium lacking calcium plus KCl (60 mM) (EC50 0.34 +/- 0.03 mM). Zeranol (8 microM) displaced the CaCl2 concentration-response curve to the right and increased the EC50 to 1.27 +/- 0.57 mM (P < 0.05) without modifying the Emax. 4. The antiestrogen tamoxifen (1 microM) and the inhibitor of cAMP-dependent protein kinase TPCK (3 microM) did not modify the effect of zeranol. However, the inhibitors of transcription (actinomycin D, 4 microM), protein synthesis (cycloheximide, 100 microM), and ornithine-decarboxilase (alpha-difluoromethyl-ornithine, 10 mM)) antagonized the effect of zeranol, increasing the IC50 to 50.2 +/- 6.2 microM, 122 +/- 6.9 microM, and 23.51 +/- 1.14 microM, respectively. 5. Our results suggest that the relaxing effect of zeranol on rat uterus smooth muscle is produced by mechanisms unrelated to cAMP and estrogen receptors, but involves transcriptional effects and polyamine synthesis.
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PMID:Transcriptional mechanisms involved in the relaxant effect of zeranol on isolated rat uterus. 914 25

To study whether cAMP-dependent transcriptional effect and polyamines might play a modulatory role on smooth muscle, the effect of forskolin on KCl (60 mM)-induced contractions in isolated rat uterus and its modification by inhibitors of cAMP-dependent protein kinase (PKA) (Rp-cAMPS and TPCK), transcription (actinomycin D), protein synthesis (cycloheximide) and ornithine decarboxylase (alpha-difluoromethyl-ornithine, DFMO), and a polyamine (spermine) have been assayed. Forskolin (0.1 to 6 microM) induced concentration-dependent relaxation on KCl-induced tonic contractions in rat uterus (IC50: 0.55 +/- 0.12 microM) which was antagonized (p<0.05) by Rp-cAMPS (30 microM), TPCK (3 microM), cycloheximide (300 microM), actinomycin D (4 and 12 microM) and TPCK (3 microM) plus actinomycin D (12 microM). The IC50 values of forskolin in the presence of these drugs were 3.75 +/- 1.53 microM, 12.08 +/- 8.18 microM, 6.88 +/- 5.02 microM, 3.80 +/- 2.35 and 5.31 +/- 2.80 microM, and 4.26 +/- 3.65 microM respectively. Furthermore, DFMO (10 mM) also shifted the relaxation curve to forskolin to the right (IC50: 3.06 +/- 2.66 microM, p<0.05) but DFMO (10 mM) plus actinomycin D (12 microM) (IC50: 1.78 +/- 1.33 microM) did not. However, DFMO (10 mM) and actinomycin D (12 microM) did not antagonize the spermine (1-30 mM)-elicited relaxation (IC50s: 7.8 +/- 0.7 mM vs 7.28 +/- 1.4 mM and 4.67 +/- 0.44 mM in the presence of DFMO and actinomycin D, respectively). Moreover, spermine (1 mM) did not decrease the forskolin induced relaxation and counteracted the antagonism produced by actinomycin D and DFMO. Our results suggest that, in rat uterus, forskolin: a) produced cAMP-dependent relaxation, as this is antagonized by Rp-cAMP and TPCK, and b) increased the activity of ornithine decarboxylase, as this is inhibited by DFMO. Therefore, polyamines could be the mediator of the cAMP-dependent transcriptional component involved in forskolin relaxation, since, as mentioned, DFMO antagonized this relaxation and spermine counteracted the displacement produced by DFMO and actinomycin D. Thus, a plasma membrane-nucleus interaction might, at least partially, explain the mechanisms involved in forskolin induced relaxation in smooth muscle of rat uterus under the present experimental conditions.
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PMID:Pharmacological evidence for the contribution of polyamines as mediators of the transcriptional component involved in smooth muscle relaxation elicited by forskolin. 941 63

The effect of kaempferol on KCI (60 mM)-induced tonic contraction in isolated rat uterus and its modification by inhibitors of cAMP-dependent protein kinase (PKA) (Rp-cAMPS and TPCK), phosphodiesterase (papaverine), adenylyl cyclase (2',3'-dideoxyadenosine, DDA), transcription (actinomycin D), protein synthesis (cycloheximide) and ornithine decarboxylase (alpha-difluoromethyl-ornithine, DFMO), as well as a polyamine, spermine, have been assayed. Kaempferol (3 to 60 microM) induced concentration-dependent relaxation on KCl-induced tonic contraction (IC50: 10.1 +/- 1.89 microM). This relaxing effect was antagonized (p<0.05) by Rp-cAMPS (10 microM), TPCK (3 microM), DDA (100 microM), actinomycin D (4 and 12 microM), cycloheximide (100 microM), DFMO (10 mM), actinomycin D (12 microM) plus TPCK and actinomycin D (12 microM) plus spermine (1 mM). Furthermore, the displacement obtained with actinomycin D plus DFMO was not statistically significant. Our results suggest that kaempferol through cAMP produces transcriptional events and polyamines are, at least partially, involved in the relaxant effect of kaempferol.
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PMID:Mechanisms involved in kaempferol-induced relaxation in rat uterine smooth muscle. 1098 69

Adenine nucleotides stimulate insulin secretion by binding to P2 receptors of the pancreatic beta-cells; the stimulus-secretion coupling is not yet clearly established and may depend on the receptor subtype. The aim of the present study was to further investigate the mechanism whereby P2Y receptor agonists enhance glucose-induced insulin secretion. Experiments were performed in rat pancreatic islets and in the INS-1 secreting cell line in the presence of a slightly stimulating glucose concentration (8.3 mmol/l). In isolated islets, the P2Y receptor agonist ADPbetaS (50 micromol/l) induced a significant fivefold increase in the cyclic AMP (cAMP) content, from 43.4+/-3.7 fmol/10 islets in controls to 210.6+/-12.0; it still induced a 4.5-fold increase in cAMP content in the absence of calcium. In another series of experiments, ADPbetaS (50 micromol/l) significantly increased glucose-induced insulin secretion from 7.7+/-0.6 ng/3 islets in controls to 11.2+/-1.0. The adenylyl cyclase inhibitor SQ 22,536 (9-[tetrahydro-2-furanyl]-9 H-purin-6-amine; 100 micromol/l), which was ineffective alone, completely prevented the stimulating effect of ADPbetaS. In a set of experiments in which ADPbetaS increased glucose-induced insulin secretion from 10.0+/-0.7 ng/3 islets to 12.6+/-0.8, the inhibitor of cAMP-dependent protein kinase, TPCK (tos-phe-chloromethylketone; 3 micromol/l), which was ineffective alone, also prevented the stimulating effect of ADPbetaS. In incubated INS-1 cells, the P2Y receptor ligand ATPalphaS increased significantly both the content of cAMP and the release of insulin, in a concentration-dependent manner in the range of 50-150 micromol/l; the insulin release was significantly correlated with the cAMP content. In conclusion, the present results show that P2Y receptor agonists, ADPbetaS and ATPalphaS, amplify glucose-induced insulin secretion by activating beta-cell adenylyl cyclase and the subsequent cAMP/protein kinase A signaling pathway.
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PMID:P2Y receptor activation enhances insulin release from pancreatic beta-cells by triggering the cyclic AMP/protein kinase A pathway. 1238 76