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:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine-adenylate cyclase response in pig skin epidermis showed a specific increase after long-term (24 h) incubation in the presence of 0.5%-1% dimethyl sulfoxide (DMSO). There was no significant difference between control and DMSO-treated epidermis with regard to cyclic AMP (cAMP) phosphodiesterase activity. DMSO had no effect on the basal cAMP levels of epidermis; beta-adrenergic and histamine-adenylate cyclase responses were not affected. The direct addition of DMSO at the time of incubation with various adenylate cyclase stimulators (adenosine, epinephrine, and histamine) had no effect on agonist-induced cAMP accumulation effects. It was concluded that DMSO affected epidermal keratinocytes during long-term incubation, resulting in a specific increase in the adenosine-adenylate cyclase response. Although the biological significance of this DMSO effect remains to be determined, it should be kept in mind when using DMSO as a solvent for various chemicals in the experiments dealing with epidermal keratinocytes in vitro.
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PMID:Dimethyl sulfoxide-induced augmentation of adenosine-adenylate cyclase response of pig skin epidermis. 243 59

Adenosine analogs were used to investigate the cellular mechanisms by which adenosine may alter renal tubular function. Cultured rabbit cortical collecting tubule (RCCT) cells, isolated by immunodissection, were treated with 5'-N-ethylcarboxamideadenosine (NECA), N6-cyclohexyladenosine (CHA), and R-N6-phenylisopropyladenosine (PIA). All three analogs produced both dose-dependent inhibition and stimulation of RCCT cell cyclic AMP (cAMP) production. Stimulation of cAMP accumulation occurred at analog concentrations of 0.1 microM to 100 microM with the rank order of potency NECA greater than PIA greater than CHA. Inhibition occurred at concentrations of 1 nM to 1 microM with the rank order of potency CHA greater than PIA greater than NECA. These effects on cAMP production were inhibited by 1,3-diethyl-8-phenylxanthine and isobutylmethylxanthine. CHA (50 nM) blunted AVP- and isoproterenol-stimulated cAMP accumulation. This modulation of hormone-induced cAMP production was abolished by pretreatment of RCCT cells with pertussis toxin. Prostaglandin E2 production was unaffected by 0.1 mM CHA. These findings indicate the presence of both inhibitory (A1) and stimulatory (A2) receptors for adenosine in RCCT cells. Moreover, occupancy of the A1 receptor causes inhibition of both basal and hormone-stimulated cAMP formation through an action on the inhibitory guanine nucleotide-binding regulatory component, Ni, of the adenylate cyclase system.
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PMID:A1 and A2 adenosine receptors in rabbit cortical collecting tubule cells. Modulation of hormone-stimulated cAMP. 243 28

The recovery of coronary flow and cardiac work was studied in isolated guinea pig hearts (working-heart preparation) after successive bolus injections of leukotriene D4 (LTD4) at increasing doses (0.01-1,000 ng). LTD4 caused an immediate (within 1 min) reduction in coronary flow and cardiac work and an increase in myocardial NADH fluorescence. There was limited spontaneous recovery at any dose and at the end of the cumulative LTD4 study, coronary flow recovered only from 41.4 +/- (SE) 3.5 (n = 10) to 53.5 +/- 4.7% of initial values, and cardiac work recovered from 21.2 +/- 4.1 to 33.1 +/- 5.6% (P less than 0.05). Adenosine (1 X 10(-6) M) or iloprost (1 X 10(-7) M) restored coronary flow but not cardiac work after LTD4 injections, in contrast to full recovery of cardiac work observed in hearts subjected to a similar degree of ischemia induced by reducing the coronary flow by a peristaltic pump, or hypoxia caused by reducing PO2 of the perfusion fluid. Adenosine (1 X 10(-6) M) and forskolin (1 X 10(-6) M) in combination, or iloprost (1 X 10(-7) M) and isoproterenol (1 X 10(-8) M) in combination, restored both coronary flow and cardiac work to control levels. Myocardial NADH levels, which increased immediately after LTD4 injections, returned to normal after perfusion with adenosine or iloprost. The data suggest that LTD4 has a prolonged vasoconstrictive effect on the heart. Reversal of this effect by compounds that stimulate adenylate cyclase of the vascular tissue (adenosine, prostacyclin) revealed a direct suppressive effect on the myocardium independent of the vascular effect and myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inducers of adenylate cyclase reverse the effect of leukotriene D4 in isolated working guinea pig heart. 243 50

The effects of adenosine and its analogues on cAMP-responses and histamine release of rat peritoneal mast cells were investigated. The adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA') activates the adenylate cyclase of the mast cell membranes and elevates the cAMP-levels of the intact mast cells. Both effects are antagonized by methylxanthines, suggesting that they are mediated via an A2 adenosine receptor. Adenosine and its analogues enhance the release of histamine from these cells, when the release is stimulated either by the calcium ionophore A 23187 or by concanavalin A. However, this effect is not antagonized by theophylline or 8-phenyltheophylline. In contrast, it is antagonized by the adenosine uptake blockers S-(p-nitrobenzyl)-6-thioinosine (NBTI) and S-(p-nitrobenzyl)-6-thioguanosine (NBTG). It is concluded that adenosine has two different effects on mast cells: it activates adenylate cyclase via an A2 adenosine receptor, and it enhances histamine release via an action at an intracellular site.
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PMID:Dual actions of adenosine on rat peritoneal mast cells. 244 Dec 69

Adenosine, applied to the coronary system of guinea pigs at up to 10(-6) M, elicits dilatation solely via an endothelium-mediated process. We investigated the role of coronary A2 receptors in this dilation, since the coronary endothelium possesses adenosine A2-receptors with a stimulatory action on the adenylate cyclase. In situ, A2 receptor stimulation can be assessed by prelabeling the coronary endothelial adenine nucleotide pool with 3H-adenosine and subsequently determining the rate of release of radiolabeled cAMP induced by A2 agonists. Thus, perfusion of isolated hearts with 5'-N-ethylcarboxamidoadenosine (NECA) dose-dependently increased coronary flow and the release of 3H-cAMP from the endothelium. In the presence of 50 microM 2',5'-dideoxyadenosine (ddA), a P-site agonist which inhibits the catalytic activity of adenylate cyclase, coronary flow increases induced by both adenosine and NECA were unaffected. In contrast, ddA reduced the release of labeled cAMP in response to NECA by about 60%. In cultured endothelial cells, ddA likewise inhibited cAMP accumulation due to NECA by about 70%. Moreover, ddA antagonized the adenylate cyclase mediated flow response due to the PGI2 analogue, iloprost, as well as the positive chronotropic and inotropic actions of isoproterenol. The dissociation elicited by ddA between the coronary flow response and the release of cAMP strongly indicates that the endothelial A2 receptors which are linked to adenylate cyclase are not causally involved in endothelium-dependent coronary dilatation induced by adenosine.
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PMID:Endothelium-mediated coronary dilatation by adenosine does not depend on endothelial adenylate cyclase activation: studies in isolated guinea pig hearts. 246 58

Rat islets were used to compare the mechanisms whereby adenosine and adrenaline inhibit insulin release. Adenosine (1 microM-2.5 mM) and its analogue N6(-)-phenylisopropyladenosine (L-PIA) (1 nM-10 microM) caused a concentration-dependent but incomplete (45-60%) inhibition of glucose-stimulated release. L-PIA was more potent than D-PIA [the N6(+) analogue], but much less than adrenaline, which caused nearly complete inhibition (85% at 0.1 microM). 8-Phenyltheophylline prevented the inhibitory effect of L-PIA and 50 microM-adenosine, but not that of 500 microM-adenosine or of adrenaline. In contrast, yohimbine selectively prevented the inhibition by adrenaline. Adenosine and L-PIA thus appear to exert their effects by activating membrane A1 receptors, whereas adrenaline acts on alpha 2-adrenergic receptors. Adenosine, L-PIA and adrenaline slightly inhibited 45Ca2+ efflux, 86Rb+ efflux and 45Ca2+ influx in glucose-stimulated islets. The inhibition of insulin release by adenosine or L-PIA was totally prevented by dibutyryl cyclic AMP, but was only attenuated when adenylate cyclase was activated by forskolin or when protein kinase C was stimulated by a phorbol ester. Adrenaline, on the other hand, inhibited release under these conditions. It is concluded that inhibition of adenylate cyclase, rather than direct changes in membrane K+ and Ca2+ permeabilities, underlies the inhibition of insulin release induced by activation of A1-receptors. The more complete inhibition mediated by alpha 2-adrenergic receptors appears to result from a second mechanism not triggered by adenosine.
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PMID:Comparison of the inhibition of insulin release by activation of adenosine and alpha 2-adrenergic receptors in rat beta-cells. 247 Mar 46

Adenosine inhibits TSH-stimulated [3H]thymidine incorporation into DNA in FRTL5 thyroid follicular cells by both inhibiting cAMP generation and acting at a locus beyond adenylate cyclase. On the other hand, adenosine markedly potentiates DNA synthesis in FRTL5 stimulated by insulin-like growth factor-I (IGF-I). The mechanisms of this latter effect are unknown, but require the coincubation of adenosine and IGF-I and not mediated by an increase in intracellular cAMP concentration. Adenosine increases the maximal response of FRTL5 to [3H]thymidine incorporation stimulated by IGF-I and increases the sensitivity of FRTL5 to IGF-I. These effects of adenosine are reflected by an increase in nuclear labeling as well as by an increase in [3H]thymidine incorporation into DNA. Adenosine also plays a role as an autocrine growth factor in FRTL5, since adenosine deaminase increases the response of these cells to TSH. The effects of adenosine on both TSH- and IGF-I-stimulated DNA synthesis are shared by guanosine and inosine, although with different potencies for the various guanine nucleosides. Inosine potentiates IGF-I-stimulated DNA synthesis, but inhibits TSH-stimulated DNA synthesis only weakly. Adenosine interacts with multiple receptors and with multiple postreceptor pathways in FRTL5 to produce divergent effects on the control of cell replication by two growth factors (TSH and IGF-I) that act through different postreceptor pathways.
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PMID:Adenosine has divergent effects on deoxyribonucleic acid synthesis in FRTL5 cells: inhibition of thyrotropin-stimulated and potentiation of insulin-like growth factor-I-stimulated thymidine incorporation. 247 35

We investigated the effects of adenosine on the positive chronotropic and inotropic responses to an endogenous catecholamine (norepinephrine), a beta 1-adrenoceptor agonist (dobutamine), an adenylate cyclase activator (forskolin), a phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, IBMX) and a calcium channel agonist (Bay k 8644) in the isolated, blood-perfused dog atrium. Each drug was injected into the sinus node artery of the isolated atrium. Adenosine infusions at low (45 or 90 nmol/min) and high (184 or 450 nmol/min) doses induced a dose-dependent decrease of sinus rate and atrial contractile force. The positive chronotropic and inotropic responses to norepinephrine, dobutamine and forskolin were dose-dependently depressed by adenosine. IBMX- and Bay k 8644-induced positive cardiac responses were also inhibited by adenosine at high doses but not at low doses. These results suggest that adenosine attenuates calcium channel-dependent as well as cyclic AMP-dependent positive chronotropic and inotropic responses to cardiostimulants in the isolated dog atrium.
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PMID:Adenosine inhibits the positive chronotropic and inotropic responses to norepinephrine and Bay k 8644 in the isolated, blood-perfused dog atrium. 248 9

We have presented a model for the role of external messenger substances in hypoxic stimulation of kidney production of erythropoietin. These autacoids probably act in concert to activate the adenylate cyclase system to enhance production and/or secretion of erythropoietin. The phosphoproteins generated in this system could act at the level of transcription and translation of erythropoietin as well as at the level of release of erythropoietin from the cell. Even though eicosanoids and beta-2-adrenergic agonists may be involved in mild to moderate hypoxia, it seems more likely that adenosine is more involved in erythropoietin production with increasing severity of hypoxia. Adenosine may play a very early role in hypoxia following the decrease in ATP to trigger erythropoietin production, and hydrogen peroxide may be generated from hypoxanthine, a metabolite of adenosine, during reoxygenation and regional changes in blood flow in the normal kidney and perhaps in certain renal and hepatic tumors. Further work is necessary in vivo to completely clarify the role of adenosine and oxygen free radicals in regulating kidney production of erythropoietin.
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PMID:External messengers and erythropoietin production. 254 24

Adenosine agonists cause a marked stimulation in cyclic AMP accumulation in whole human retinal pigment epithelial (RPE) cells in the presence of adenosine deaminase and papaverine, a phosphodiesterase inhibitor. N-Ethylcarboxamidoadenosine (NECA) stimulates cyclic AMP accumulation 16.1-fold above basal with an EC50 of 2.5 x 10(-7) M. It is also an effective (1.9-fold) stimulator of adenylate cyclase activity in RPE membrane preparations and a modest (1.22-fold) stimulator in the presence of forskolin in RPE cell membranes prepared from freshly isolated porcine RPE. N6-Cyclopentyladenosine (CPA) and N6-phenylisopropyladenosine (PIA) also increase cyclic AMP levels with EC50s of 4.9 x 10(6) M (8.9-fold above basal) and 3.5 x 10(-6) M (8.0-fold above basal) respectively. This potency order (NECA greater than PIA greater than CPA) is typical of A2-adenosine receptors. The relatively A1-selective agonists 10(-7) M indicating that RPE cells do not have A1-receptors which inhibit adenylate cyclase. Three adenosine receptor antagonists, BW-A1433U, 8-cyclopentyltheophylline and 8-sulfophenyltheophylline, blocked the NECA-induced stimulation of cyclic AMP accumulation with IC50s of 0.36 microM, 1.5 microM, and 75 microM respectively. Since alteration of cAMP levels has been demonstrated to affect several RPE functions, including cell migration, resorption of subretinal fluid, and phagocytosis, adenosine may play a significant regulatory role in RPE.
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PMID:Human retinal pigment epithelial cells in culture possess A2-adenosine receptors. 254 54


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