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

---

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

The receptors responsible for the adenosine-mediated control of acetylcholine release from immunoaffinity-purified rat striatal cholinergic nerve terminals have been characterized. The relative affinities of three analogues for the inhibitory receptor were (R)-phenylisopropyladenosine greater than cyclohexyladenosine greater than N-ethylcarboxamidoadenosine (NECA), with binding being dependent of the presence of Mg2+ and inhibited by 5'-guanylylimidodiphosphate [Gpp(NH)p] and adenosine receptor antagonists. Adenosine A1 receptor agonists inhibited forskolin-stimulated cholinergic adenylate cyclase activity, with an IC50 of 0.5 nM for (R)-phenylisopropyladenosine and 500 nM for (S)-phenylisopropyladenosine. A1 agonists inhibited acetylcholine release at concentrations approximately 10% of those required to inhibit the cholinergic adenylate cyclase. High concentrations (1 microM) of adenosine A1 agonists were less effective in inhibiting both adenylate cyclase and acetylcholine release, due to the presence of a lower affinity stimulatory A2 receptor. Blockade of the A1 receptor with 8-cyclopentyl-1,3-dipropylxanthine revealed a half-maximal stimulation by NECA of the adenylate cyclase at 10 nM, and of acetylcholine release at approximately 100 nM. NECA-stimulated adenylate cyclase activity copurified with choline acetyltransferase in the preparation of the cholinergic nerve terminals, suggesting that the striatal A2 receptor is localized to cholinergic neurones. The possible role of feedback inhibitory and stimulatory receptors on cholinergic nerve terminals is discussed.
...
PMID:Both A1 and A2a purine receptors regulate striatal acetylcholine release. 235 24

Effects of chronic exposure of cultured atrial myocytes to R-N6-(2-phenylisopropyl)-adenosine (R-PIA) on the A1 adenosine receptor-mediated inhibition of adenylate cyclase activity and myocyte contractility were examined. Chronic exposure of atrial myocytes cultured from 14-day-old chick embryos to R-PIA desensitized the myocyte to the inhibitory effects of R-PIA on contractility and adenylate cyclase activity in a time- and dose-dependent manner. Desensitization of the negative inotropic response was only partial, whereas the adenosine receptor-mediated inhibition of adenylate cyclase activity was almost completely absent after 24 hours of R-PIA (1 microM) exposure. Furthermore, the contractile response to R-PIA desensitized more slowly than the desensitization of A1 adenosine receptor-mediated inhibition of adenylate cyclase (t1/2 = 11.4 +/- 0.7 hours versus 7.5 +/- 1 hours, mean +/- SEM, n = 12 and 6, respectively). Thus, the two A1 adenosine receptor-linked functional responses desensitized differently in response to chronic exposure of the myocyte to R-PIA. Binding of the antagonist radioligand [3H]-8-cyclopentyl-1,3-dipropylxanthine [( 3H]CPX) in membranes from myocytes preexposed to R-PIA demonstrated a time-dependent decrease in receptor density without any change in the affinity for the antagonist radioligand. Computer analyses of agonist competition with [3H]CPX binding in membranes from control and R-PIA-treated myocytes revealed a conversion of the high-affinity A1 adenosine receptor to a low-affinity form such that after 24 hours of 1 microM R-PIA exposure, all of the receptors were in a low-affinity form.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Differential desensitization of A1 adenosine receptor-mediated inhibition of cardiac myocyte contractility and adenylate cyclase activity. Relation to the regulation of receptor affinity and density. 237 79

Rat platelets and adipocytes were used as models to investigate alterations of the A2- and of the A1-adenosine receptor-adenylate cyclase system of peripheral cells caused by chronic caffeine administration. The maximum effects of 5'-N-ethylcarboxamidoadenosine (NECA) to stimulate adenylate cyclase activity in suspensions of platelet membranes and to inhibit aggregation were significantly greater with platelets from caffeine-treated rats than from control rats. The effects of 1 to 100 nM prostaglandin E1 to inhibit platelet aggregation and to stimulate adenylate cyclase activity in platelet membranes were also significantly greater with caffeine-treated than with control rats. These data suggest that the increased ability of NECA to inhibit platelet aggregation after chronic caffeine ingestion was a result of increased cyclic AMP accumulation induced by this agonist. The increased stimulatory effect of NECA on adenylate cyclase in platelet membranes could be due to an increased A2-adenosine receptor number and/or an increased functional coupling between A2-adenosine receptor and stimulatory guanine nucleotide binding proteins. In contrast, although A1-receptor number was 37% higher in fat cell membranes from caffeine-treated rats than in those from control rats, increased A1-adenosine receptor-mediated inhibition of lipolysis and of adenylate cyclase was not detected. Thus, chronic caffeine consumption causes alterations in the response of some but not all peripheral cell types to agonists of adenosine receptors.
...
PMID:The effects of chronic caffeine administration on peripheral adenosine receptors. 239 10

An adenosine receptor has been characterized to unambiguously demonstrate that the inhibitory guanine nucleotide regulatory protein, Gi, of 1321N1 human astrocytoma cells is fully capable of functionally coupling to adenylate cyclase. Adenosine receptor agonists attenuated cyclic AMP accumulation by 35 to 75% with the order of potency of N6(R-phenylisopropyl)-adenosine greater than adenosine = 2-chloroadenosine greater than N6-methyladenosine = N6-benzyladenosine. 3-Isobutyl-1-methylxanthine competitively antagonized the effect of adenosine receptor agonists. Adenylate cyclase activity measured in cell-free preparations from 1321N1 cells was inhibited by N6(R-phenylisopropyl)-adenosine. Pretreatment of 1321N1 cells with pertussis toxin blocked both adenosine receptor-mediated inhibition of adenylate cyclase activity and attenuation of cyclic AMP accumulation. In contrast to the effects on responses to adenosine receptor agonists, 3-isobutyl-1-methylxanthine noncompetitively antagonized muscarinic receptor-mediated attenuation of cyclic AMP accumulation and pertussis toxin had no effect. These data are consistent with the ideas that Gi is fully functional in 1321N1 cells and links inhibitory adenosine receptors to adenylate cyclase, and that the muscarinic receptor of these cells couples to the phosphoinositide response system, but is incapable of functionally coupling through Gi to inhibit adenylate cyclase.
...
PMID:Adenosine and muscarinic cholinergic receptors attenuate cyclic AMP accumulation by different mechanisms in 1321N1 astrocytoma cells. 242 Sep 67

Adenosine and several of its analogues produced a concentration-dependent shortening of calcium-dependent action potential (c.a.p.) duration of mouse dorsal root ganglion (d.r.g.) neurones in dissociated cell culture. The following rank order of potency was obtained: N6-(L-phenylisopropyl)adenosine greater than N6-(D-phenylisopropyl)adenosine greater than N6-cyclohexyladenosine greater than 2-chloroadenosine much greater than 1-methylisoguanosine greater than adenosine. Effects of adenosine agonists on c.a.p. duration were blocked by methylxanthine adenosine antagonists. Adenosine monophosphate (AMP) and cyclic AMP shortened c.a.p.s in d.r.g. neurones, while ATP also depolarized cells. Voltage-clamp analysis revealed that the effect arose from reduction of a voltage-dependent calcium conductance. Adenosine agonists reduced depolarization-evoked inward currents but did not alter membrane conductance following blockade of calcium channels by cadmium. Additionally, adenosine reduced the instantaneous current-voltage slope (chord conductance) during step commands that produced maximal activation of voltage-dependent calcium conductance. If effects of adenosine on neuronal somata and synaptic terminals are similar, adenosine agonists may inhibit neurotransmitter release in the central nervous system by inhibiting a voltage-dependent calcium conductance. Since effects of adenosine agonists did not correspond with their relative potencies as modulators of adenylate cyclase activity or inhibitors of neurotransmitter release in peripheral tissues, a novel adenosine receptor may be involved in regulation of this conductance.
...
PMID:Adenosine agonists reduce voltage-dependent calcium conductance of mouse sensory neurones in cell culture. 242 Sep 81

[3H]Phenylisopropyladenosine ([3H]PIA) was used to characterize adenosine receptor sites in a sarcolemma-enriched membrane fraction from canine ventricle. Specific [3H]PIA binding to the cardiac membrane preparation was rapid, readily reversible, and saturable with increasing free ligand concentrations. Scatchard analysis indicated a single class of binding sites having a Bmax of 601 fmol/mg protein. The Kd of [3H]PIA for its binding site was 52-85 nM as determined independently from kinetic and equilibrium studies, respectively. Binding was stereospecific in that (-)PIA was ninefold more potent than (+)PIA in competing for [3H]PIA binding sites. Adenosine receptor agonists such as N6-cyclohexyladenosine, (-)PIA, 2-chloroadenosine, N6-methyladenosine, and adenosine-5'-ethylcarboxamide were the most potent agents found to compete for [3H]PIA binding sites and displayed IC50 values of 14-224 nM, while 2',5'-dideoxyadenosine, a potent P-site agonist, inhibited binding only weakly. Alkylxanthines also inhibited [3H]PIA binding with relative potency relationships that paralleled their known pharmacological activity as adenosine receptor antagonists. (-)PIA inhibited activation of membrane adenylate cyclase by isoproterenol in a concentration-dependent manner with a maximum of 22% inhibition occurring at 1 microM PIA. It is concluded that the specific binding of [3H]PIA to the sarcolemma-enriched fraction of canine ventricle represents an Ri adenosine receptor on the surface of the myocardial cell. Such a receptor has been postulated to mediate the adenosine-induced attenuation of the effects of catecholamines on intact ventricular myocardium.
...
PMID:Adenosine receptors in an enriched fraction of plasma membranes from canine ventricular myocardium. 242 82

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.
...
PMID:Dual actions of adenosine on rat peritoneal mast cells. 244 Dec 69

We have confirmed our previous (Fredholm et al. 1986a) finding that the dihydropyridine calcium channel agonist Bay K 8644 can displace [3H]-R-PIA from its binding site, the adenosine A1-receptor. Bay K 8644 had an apparent Ki of 5.2 X 10(-6) M. The effect was shared by the two dihydropyridine calcium channel antagonists nifedipine and felodipine (Ki 4.2 and 8.7 X 10(-6) M, respectively). By contrast, two non-dihydropyridine calcium channel antagonists, verapamil and diltiazem, did not affect binding. Bay K 8644 displaced [3H]-R-PIA from its binding sites in a solubilized preparation. [3H]-XAC, a novel, potent A1-receptor antagonist ligand, was also displaced by the dihydropyridine compounds with a similar or slightly higher potency as the displacement of R-PIA. This suggests a direct interaction with the adenosine receptor rather than an effect on regulatory GTP-binding proteins. However, at 1 mumol/l neither Bay K 8644 nor nifedipine significantly attenuated cyclic AMP accumulation in rat hippocampi or the R-PIA-mediated adenylate cyclase inhibition. The results show that dihydropyridine compounds that act as agonists or antagonists on L-type calcium channels can also affect adenosine receptors. The potency of the compounds for this effect is much lower than their potency as calcium channel agonists or antagonists. The results may therefore be of more experimental than clinical significance.
...
PMID:Interaction of dihydropyridine calcium channel agonists and antagonists with adenosine receptors. 244 63

Friend virus-transformed mouse erythroleukemia (MEL) cells can be induced to undergo erythroid differentiation by a variety of compounds, including dimethyl sulfoxide (DMSO) and the adenosine analog xylosyladenine. The present studies have monitored the effects of the stable adenosine receptor ligand N6-phenylisopropyladenosine (PIA) on induction of MEL cell differentiation. PIA has been previously shown to stimulate adenylate cyclase activity in rat hepatic and mouse Leydig 1-10 cells as well as inhibit adenylate cyclase in adipocytes. In the present study, PIA was ineffective as an inducer of the differentiated MEL cell phenotype. However, the results demonstrate that PIA inhibits the induction of MEL cell differentiation by DMSO and xylosyladenine. The extent of this inhibition as determined by benzidine staining, induction of globin RNA, and loss of self-renewal capacity was dependent on PIA concentration. The results also demonstrate that PIA induces a rapid and sustained increase in cyclic AMP (cAMP) levels. Furthermore, there was a highly significant correlation between cAMP levels and inhibition of xylosyladenine-induced differentiation (r = 0.962, P less than 0.0005). This relationship is further supported by the demonstration that prostaglandins E1 and E2 increase MEL cell cAMP levels and inhibit induction of the differentiated MEL cell phenotype. Moreover, PIA inhibited induction of MEL cell differentiation by butyric acid, diazepam, hypoxanthine, and the aminonucleoside analog of puromycin. These results suggest that cAMP may act as a negative regulatory signal in the induction of MEL cell differentiation.
...
PMID:Modulation of cyclic AMP levels and differentiation by adenosine analogs in mouse erythroleukemia cells. 245 Aug 78

1. Depolarization of excitable cells of the central nervous system results in the formation of the second messengers cyclic AMP, cyclic GMP, inositol phosphates, and diacylglycerides. 2. Depolarization-evoked accumulation of cyclic AMP in brain preparations can be accounted for mainly by the release of adenosine, which subsequently interacts with stimulatory adenosine receptor linked to adenylate cyclase. 3. Depolarization-evoked formation of cyclic GMP in brain preparations is linked to activation of voltage-dependent calcium channels, presumably leading to activation of guanylate cyclase by calcium ions. 4. In brain slices depolarization-evoked stimulation of phosphoinositide breakdown and subsequent formation of inositol phosphates and diacylglycerides are linked to activation of voltage-dependent calcium channels, which are sensitive to dihydropyridines, presumably leading to activation of phospholipase(s) C by calcium ions. 5. In the synaptoneurosome preparation depolarization-evoked stimulation of phosphoinositide breakdown does not involve activation of dihydropyridine-sensitive calcium channels and, instead, appears to be regulated primarily by the intracellular concentration of sodium ions. Thus, agents that induce increases in intracellular sodium--such as toxins that open or delay inactivation of voltage-dependent sodium channels; ouabain, an inhibitor of Na+/K+ ATPase that transports sodium outward and a sodium ionophore--all stimulate phosphoinositide breakdown. Mechanistically, increases in intracellular sodium either might directly affect phospholipase(s) C or might lead to influx of calcium ions through Na+/Ca2+ transporters. 6. Depolarization-evoked stimulation of cyclic AMP formation and phosphoinositide breakdown can exhibit potentiative interactions with responses to receptor agonists, thereby providing mechanisms for modulation of receptor responses by neuronal activity. 7. Since all these second messengers can induce phosphorylation of ion channels through the activation of specific kinases, it is proposed that depolarization-evoked formation of second messengers represents a putative feedback mechanism to regulate ion fluxes in excitable cells.
...
PMID:Formation of second messengers in response to activation of ion channels in excitable cells. 245 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---