Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human peripheral blood mononuclear cells (H-PBMC) from 10 healthy donors were stimulated to proliferate with phytohemagglutinin lectin (PHA), anti-CD3 monoclonal antibody (mAb), and anti-CD3 mAb plus phorbol 12, myristate 13 acetate (TPA), a protein kinase C (PKC) agonist. Anti-CD3 mAb-mediated mitogenesis was 35-75% of that observed with PHA. When TPA was added to a dose of mAb that by itself did not cause mitogenesis, proliferation equal to 50-90% of the maximally mitogenic dose occurred. TPA did not enhance proliferation with maximally mitogenic doses of antibody. Dimethyl-prostaglandin E2, dibutyryl cyclic AMP, and forskolin (an adenyl cyclase agonist) inhibited PHA, anti-CD3, and anti-CD3/PMA-mediated mitogenesis. Cyclosporine (CSA) inhibited anti-CD3 and anti-CD3/TPA mitogenesis in a dose-dependent fashion. While CSA inhibited anti-CD3 and anti-CD3/TPA mitogenic signals, it did not affect PGE2 production by anti-CD3 mAb-stimulated H-PBMC. In the presence of CSA, PGE2 production in PHA-stimulated H-PBMC was increased. PGE2 inhibits lymphocyte proliferation via a cyclic AMP-mediated mechanism and may enhance maturation of suppressor cells. CSA inhibits anti-CD3 mAb and anti-CD3/TPA proliferative signals in H-PBMC yet has no effect or may even enhance production of suppressive PGE2. The maturation of antigen-specific suppressor cells elicited by CSA may involve active down-regulation of CD3 receptor and PKC-dependent events while PGE2 production continues.
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PMID:Cyclosporine effect on anti-CD3 monoclonal antibody-stimulated mitogenesis, phorbol ester comitogenesis, and PGE2 production. 182 79

The process of signal transduction by interleukin 1 (IL-1) or tumor necrosis factor alpha (TNF alpha) for the production of hematopoietic growth factors by cultured fibroblasts was studied using inhibitors for protein kinase C, cyclic nucleotide-dependent protein kinases, calmodulin-dependent protein kinases, and the Na(+)-H+ antiport system. The protein kinase C inhibitor H-7 was shown to inhibit both IL-1 beta- and TNF alpha-induced granulocyte-macrophage colony-stimulating activity (GM-CSA) production and release from cultured fibroblasts in a dose-dependent manner, with 40 microM H-7 demonstrating maximum suppression of the GM-CSA response. In addition, 100-200 nM staurosporine, a more potent inhibitor of protein kinase C, also completely suppressed GM-CSA from IL-1 beta- and TNF alpha-induced fibroblasts. In contrast, a potent inhibitor of cyclic nucleotide-dependent protein kinases, HA1004, showed no effect when used at 10-40 microM. In addition, an inhibitor of calmodulin-induced protein kinases, W-7, also showed no effect when used at 10-30 microM. Prior incubation with H-7 did not inhibit the ability of fibroblasts to subsequently respond to IL-1 beta or TNF alpha, nor did H-7 directly inhibit the granulocyte-macrophage colony-forming assay. Both dibutyryl cyclic adenosine monophosphate (10-30 microM) and forskolin (1-100 nM), activators of adenylate cyclase, in the presence or absence of the phosphodiesterase inhibitor isobutylmethylxanthine, failed to stimulate a GM-CSA response from cultured fibroblasts, indicating a lack of effect of cyclic nucleotide-dependent protein kinases. Furthermore, the addition of H-7 30 min after induction with IL-1 beta or TNF alpha showed little effect on the synthesis of GM-CSA by cultured fibroblasts, indicating that the signal transduction process probably occurred within the first 30 min of ligand-receptor interaction. Finally, amelioride, an inhibitor of the Na(+)-H+ antiport, was shown to inhibit IL-1 beta-induced GM-CSA in a dose-dependent manner.
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PMID:The role of protein kinase C in interleukin 1 and tumor necrosis factor alpha induction of fibroblasts to produce and release granulocyte-macrophage colony-stimulating activity. 216 34

The excitatory amino acid (EAA), L-cysteine sulfinic acid (L-CSA), elicited a dose-dependent increase in cAMP accumulation in adult rat hippocampus that was not blocked by ionotropic glutamate receptor antagonists. Therefore, the possibility was examined that L-CSA activates the (1S,3R)-amino-1,3-cyclopentanedicarboxylic acid (1S,3R-ACPD)-sensitive metabotropic glutamate receptor (mGluR) that increases cAMP by potentiating responses elicited by adenosine or other agonists of receptors coupled to adenylate cyclase via Gs. Like 1S,3R-ACPD, L-CSA induced a cAMP response that was inhibited by the adenosine receptor antagonist, 8-para-sulfyltheophylline, and by adenosine deaminase. In contrast to the 1S,3R-ACPD-induced cAMP response, the L-CSA-induced response was not potentiated by the adenosine uptake inhibitor, dipyridamole. Taken together with the previous finding that L-CSA does not potentiate cAMP responses elicited by agonists of receptors that activate Gs, these data suggest that L-CSA increases cAMP accumulation by activating a metabotropic EAA receptor that is different from the 1S,3R-ACPD-sensitive mGluR associated with potentiation of cAMP responses.
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PMID:An L-cysteine sulfinic acid-sensitive metabotropic receptor mediates increased cAMP accumulation in hippocampal slices. 773 95