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)

The induction of cytolytic activity in PC60, a murine T-cell hybridoma, is paralleled by a rise in the level of BLT-esterase (N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl esterase), a serine esterase specific for activated T-cells. Both interleukin-1 (IL-1) and dibutyryl cAMP were albe to increase the esterase activity in a dose-dependent and saturable manner. When added in combination the two activators showed a strong synergism: BLT-esterase levels were up to three times higher than the sum of the levels due to dibutyryl cAMP and IL-1 added separately. Stimulators of the adenylate cyclase, such as forskolin and cholera toxin, induced a similar enhancement of the BLT-esterase response to IL-1. PC60 cells did not produce any cAMP in response to IL-1. When the two stimuli were added sequentially a second effect for cAMP emerged: preincubation with dibutyryl cAMP or activators of the adenylate cyclase for 4 h or longer completely blocked the action of subsequently added IL-1. Taken together, the data demonstrate a dual modulatory role for cAMP in T-lymphocytes activated by IL-1.
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PMID:Cyclic AMP modulates interleukin-1 action in a cytotoxic T-cell hybridoma. 217 20

Adenosine and ATP have been shown to activate separate cell surface purinergic receptors which have been designated P1 for adenosine and P2 for ATP. The pharmacological characterization of P1 and P2 purinergic receptor-mediated signal transduction has been performed in cultured cell lines of the ciliary epithelium. In ODM Clone-2, a cell line derived from human nonpigmented ciliary epithelium (NPE) and in a clone derived from bovine pigmented ciliary epithelium (PE), we observed that adenosine inhibits adenylate cyclase activity at high potency (nM) and stimulates adenylate cyclase activity at low potency (microM) suggesting the presence of P1 subtypes on these cell membranes. The selective agonist cyclopentyladenosine (CPA) was effective at inhibiting forskolin-stimulated adenylate cyclase in these cells. The IC50 for CPA in both NPE and PE was approximately 1 nM in the absence, and 11 nM in the presence of 3-isobutyl-1-methylxanthine (IBMX). In NPE, the selective agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS 21680) stimulated adenylyl cyclase with an EC50 of 11 +/- 4 nM in the presence of 4-(3-butoxy-4-methyoxybenzyl)-2-imidazolidinone (RO-20-1724), a phosphodiesterase inhibitor devoid of adenosine receptor antagonism, and 61 +/- 8 microM in the presence of IBMX. In PE cells, EC50 value of RO-20-1724 was 19 +/- 5 nM (n = 3). The characterization of P2 receptors based upon the ability of ATP and its related analogues to stimulate inositol phosphate production reveal the presence of a putative P2u receptor in both cell types.
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PMID:Purinergic receptors in ocular ciliary epithelial cells. 840 76

The modulation of the high-voltage-activated calcium current (ICa) by external ATP was examined in single ventricular cardiomyocytes of the hamster using the whole-cell configuration of the patch-clamp technique. Extracellular application of ATP (0.1-100 microM) was found to inhibit ICa reversibly. The inhibition followed a slow time course (half time approximately 25 s) and was accompanied by very small changes of the holding current and no shift in the current-voltage relationship. With 100 microM ATP, peak ICa was reduced by approximately 30%. This response was not blocked by the P1 inhibitor 8-cyclopentyl-1,3-dipropylxanthine. The nonhydrolyzable ATP analogs adenosine 5'-O-(3-thiotriphosphate) and AMP-adenosine 5'-[beta,gamma-imido]triphosphate also reduced ICa. The ATP analog alpha,beta-methylene-ATP was about equipotent with ATP at 50 microM. Internal guanosine 5'-O-(3-thiotriphosphate) (200 microM) rendered the ATP-mediated inhibition of ICa poorly reversible, whereas internal guanosine 5'-O-(2-thiodiphosphate) (200-500 microM) had no effect. Holding the intracellular adenosine 3',5'-cyclic monophosphate concentration at a constant high level did not alter the ATP response. We conclude that external ATP inhibits ICa via a P2 purinergic receptor in hamster ventricular myocytes. Our results suggest the involvement of a G protein not coupled to adenylate cyclase. The inhibition of ICa by extracellular ATP might have pathophysiological relevance under conditions of myocardial injury.
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PMID:Inhibition of the voltage-dependent calcium current by extracellular ATP in hamster ventricular cardiomyocytes. 924 97

Resolvin E1 (RvE1) is a potent anti-inflammatory and proresolving mediator derived from omega-3 eicosapentaenoic acid generated during the resolution phase of inflammation. RvE1 possesses a unique structure and counterregulatory actions that stop human polymorphonuclear leukocyte (PMN) transendothelial migration and PMN infiltration in several murine inflammatory models. To examine the mechanism(s) underlying anti-inflammatory actions on PMNs, we prepared [(3)H]RvE1 and characterized its interactions with human PMN. Results with membrane fractions of human PMN demonstrated specific binding with a K(d) of 48.3 nM. [(3)H]RvE1 specific binding to human PMN was displaced by leukotriene B(4) (LTB(4)) and LTB(4) receptor 1 (BLT1) antagonist U-75302, but not by chemerin peptide, a ligand specific for another RvE1 receptor ChemR23. Recombinant human BLT1 gave specific binding with [(3)H]RvE1 with a K(d) of 45 nM. RvE1 selectively inhibited adenylate cyclase with BLT1, but not with BLT2. In human PBMC, RvE1 partially induced calcium mobilization, and blocked subsequent stimulation by LTB(4). RvE1 also attenuated LTB(4)-induced NF-kappaB activation in BLT1-transfected cells. In vivo anti-inflammatory actions of RvE1 were sharply reduced in BLT1 knockout mice when given at low doses (100 ng i.v.) in peritonitis. In contrast, RvE1 at higher doses (1.0 mug i.v.) significantly reduced PMN infiltration in a BLT1-independent manner. These results indicate that RvE1 binds to BLT1 as a partial agonist, potentially serving as a local damper of BLT1 signals on leukocytes along with other receptors (e.g., ChemR23-mediated counterregulatory actions) to mediate the resolution of inflammation.
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PMID:Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. 1733 91