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 enhanced histamine release and prolonged the adenosine 3':5'-cyclic monophosphate (cyclic AMP) response in purified rat peritoneal mast cells following immunological challenge. The effect on the cyclic AMP response, which was blocked by 8-phenyltheophylline, probably results from an interaction with A2-purinoceptors. Enhancement of histamine release showed different characteristics. It was not inhibited by dipyridamole or hexobendine, thereby indicating an action at the cell surface. However, the relative potencies of adenosine analogues and nucleotides, together with the observation that this effect was not antagonized by 8-phenyltheophylline or theophylline, suggest that it is not mediated by a previously recognised purinoceptor. Thus, enhancement of histamine release may represent a novel cell surface action of adenosine which is independent of its effects on adenylate cyclase.
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PMID:Adenosine potentiates immunological histamine release from rat mast cells by a novel cyclic AMP-independent cell-surface action. 241 20

An adenosine-sensitive adenylate cyclase has been demonstrated in anterior pituitary cultured cells in the present studies. N-ethylcarboxamideadenosine (NECA), L-N6-phenylisopropyladenosine (PIA), and 5'-N-methylcarboxamideadenosine (MECA), all stimulated adenylate cyclase in a concentration-dependent manner in the order of potency NECA greater than PIA greater than MECA. Adenosine showed a biphasic effect on adenylate cyclase: stimulation at lower and inhibition at higher concentrations, whereas 2'-deoxyadenosine only inhibited adenylate cyclase in a concentration-dependent manner. The stimulatory effect of NECA on adenylate cyclase was dependent on metal ion concentrations and was blocked by 3-isobutyl-1-methylxanthine and 8-phenyltheophylline. Various agonists such as isoproterenol, prostaglandins (PGE1), vasoactive intestinal peptide, corticotropin-releasing factor, NaF, and forskolin, all stimulated adenylate cyclase to various degrees. The stimulatory effect of vasoactive intestinal peptide and corticotropin-releasing factor on adenylate cyclase was found to be almost additive with the stimulation exerted by NECA. These data indicate the presence of adenosine stimulatory receptors ('Ra') in anterior pituitary which are coupled to adenylate cyclase. It is possible that adenosine may act as one of the important regulators to regulate and/or modulate the effects of agents/factors in the release of pituitary hormones.
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PMID:Adenosine-sensitive adenylate cyclase in rat anterior pituitary. 241 83

Adenosine produced a concentration-related enhancement of antigen-induced 5-hydroxytryptamine (5-HT) release from rat serosal mast cells. This potentiation was maximal following the simultaneous addition of adenosine with antigen. Enhancement of 5-HT release was accompanied by potentiation of the adenosine 3':5'-cyclic monophosphate (cyclic AMP) response to challenge. The cyclic AMP response, which was antagonized by 8-phenyltheophylline, was characterized as an A2-purinoceptor-mediated effect by the use of 5'-N-ethylcarboxamideadenosine (NECA) and L-N6-phenylisopropyladenosine (L-PIA). Enhancement of 5-HT release, conversely, was not blocked by 8-phenyltheophylline suggesting it to be mediated by a cyclic AMP-independent mechanism. The effect of adenosine on 5-HT release was not reduced by the inhibition of the facilitated uptake of adenosine with dipyridamole, hexobendine or p-nitrobenzylthioguanosine, therefore, suggesting it to be mediated by a cell surface receptor. The receptor mediating enhancement of 5-HT does not appear to belong to the P2-purinoceptor subtype as adenosine was more potent than both adenosine monophosphate (AMP) and adenosine diphosphate (ADP) and alpha, beta-methylene ATP was inactive. Furthermore, the effects of AMP were blocked by alpha, beta-methylene ADP, which inhibits the conversion of AMP to adenosine. Adenosine, NECA, L- and D-PIA were all of equal potency in enhancing 5-HT release. Inosine and 3-deazaadenosine were also active. The rank order of potency of these adenosine analogues is not consistent with an effect at A1- or A2-purinoceptors. There appear to be two adenosine receptors on rat mast cells, an A2-purinoceptor which stimulates adenylate cyclase and a separate purinoceptor, stimulation of which produces enhancement of mediator release by an unknown mechanism. The effects mediated by these receptors appear to be independent of each other.
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PMID:Studies on the receptor mediating cyclic AMP-independent enhancement by adenosine of IgE-dependent mediator release from rat mast cells. 242 Apr

Adenosine stimulates and inhibits adenylate cyclase activity and cAMP levels in WI-38 and VA13 fibroblasts. The inhibitory effects appear to be mediated by both A1 receptors and the P-site. Results supporting these conclusions are as follows: Adenosine by itself increased cAMP accumulation in these cells. PGE1-stimulated cAMP accumulation was inhibited by adenosine in a concentration-dependent fashion. IAP treatment blocked adenosine inhibition of cAMP accumulation and adenylate cyclase activity and enhanced adenosine stimulation of cAMP accumulation in VA13 cells. Theophylline and MIX attenuated adenosine inhibition of cAMP accumulation. Adenosine analogs with substitutions in the purine ring inhibited PGE1-stimulated cAMP accumulation and adenylate cyclase activity. PGE1-stimulated cAMP accumulation was inhibited by the P-site agonist 2'5'-dideoxyadenosine, but this inhibition was not attenuated by MIX or IAP treatment. These data support the idea that adenosine may inhibit cAMP accumulation in VA13 or WI-38 cells by acting at an A1 receptor of the P-site. The decrease in cAMP accumulation mediated by the A1 receptor appeared to be due at least in part to an Ni-mediated inhibition of adenylate cyclase.
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PMID:A1 and A2 adenosine receptors regulate adenylate cyclase in cultured human lung fibroblasts. 242 Jun 58

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.
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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.
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PMID:Adenosine agonists reduce voltage-dependent calcium conductance of mouse sensory neurones in cell culture. 242 Sep 81

Cyclic adenosine 3',5'-monophosphate (cAMP) is known to mediate mammalian sperm function. Progress in understanding the mechanism of the control of cAMP levels in mammalian sperm has been hampered, however, by an inability to identify a physiological regulator of adenylate cyclase. In this report we provide evidence that adenosine, 2'-deoxyadenosine, and a number of other adenosine analogues that activate adenylate cyclase in other tissues stimulate bovine caudal sperm motility, and we suggest that they do so through elevation of cAMP levels. We have demonstrated that these compounds elevate cAMP levels in and stimulate the motility of mature bovine caudal sperm in the same concentration range (20-300 microM). In addition, we report that these same nucleosides, under appropriate conditions, elevate cAMP levels and initiate motility in immature caput sperm. Adenosine analogue structure-activity relationships carried out with caudal sperm indicate that substitution at position 2 in the purine ring in the adenosine molecule leads to enhanced activity, while substitution at the N-6 amino group reduces potency. Nucleosides that do not stimulate motility in caudal sperm do not elevate cAMP levels. We postulate that adenosine is a physiological regulator of sperm motility and suggest that it and its analogues owe their action to elevation of cAMP levels.
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PMID:Regulation of bovine sperm motility and cyclic adenosine 3',5'-monophosphate by adenosine and its analogues. 242 88

[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.
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PMID:Adenosine receptors in an enriched fraction of plasma membranes from canine ventricular myocardium. 242 82

Adenosine 3',5-cyclic monophosphate (cAMP) was shown to stimulate insulin secretion from electrically permeabilised islets of Langerhans incubated in Ca2+/EGTA buffers. cAMP-induced insulin secretion occurred in the presence of either sub-stimulatory (50 nM) or stimulatory (greater than 100 nM) concentrations of Ca2+. Similar effects on secretion were obtained in response to 8-bromo-cAMP (8-Br-cAMP) or the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine. Forskolin (0.2-20 microM) increased adenylate cyclase activity and enhanced insulin secretion from the permeabilised islets. These results suggest that, in electrically permeabilised islets, cAMP-induced insulin secretion is not dependent on changes in cytosolic Ca2+.
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PMID:Regulation of insulin secretion by cAMP in rat islets of Langerhans permeabilised by high-voltage discharge. 242 66

Effects of adenosine analogs on ACTH-stimulated adenylate cyclase activity and steroidogenesis in rat adrenocortical glands have been studied. Adenosine analogs inhibited ACTH-stimulated adenylate cyclase activity by a GTP-dependent process. Methylxanthines reversed the inhibitory effect of N6-phenyl-isopropyl-adenosine (PIA), but not of 2',5'-dideoxy-adenosine. These results suggest that adenosine negatively regulates the stimulation of adenylate cyclase by ACTH at the external and the internal site of the membrane. The inhibitory effect of PIA on ACTH-stimulated steroidogenesis by isolated cells was antagonized by methylxanthines. PIA also inhibited steroidogenesis induced by dibutyryl cAMP, suggesting an inhibitory action of the nucleoside distal to the cAMP system. These results suggest the presence of a common site located in the external membrane for adenosine which subsequently mediates two independent processes, one is negatively coupled to the adenylate cyclase and the other to steroidogenesis for negative feedback controls of the adrenal cortex.
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PMID:Inhibition by adenosine of ACTH-stimulated adenylate cyclase and steroidogenesis in the adrenal cortex. 242 72


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