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Cyclase

About: Cyclase is a research topic. Over the lifetime, 10162 publications have been published within this topic receiving 388566 citations.


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Journal Article
TL;DR: This compound blocked WIN 55212-2-mediated inhibition of N-type calcium channels and activation of inwardly rectifying potassium channels in N18 and AtT-20-CB2 cells, respectively.
Abstract: LY320135 is a selective antagonist for the brain CB1 receptor, having greater than 70-fold higher affinity for the CB1 than the peripheral CB2 receptor. The K i values for LY320135 at the CB1 and CB2 receptors, transfected and stably expressed in cell lines, were 224 nM and >10 μM, respectively. Similar K i values were measured in binding studies performed on cerebellum and spleen membrane preparations endogenously expressing the CB1 (203 nM) and CB2 (>10 μM) receptors, respectively. LY320135 functionally reversed anandamide-mediated adenylate cyclase inhibition in Chinese hamster ovary (CHO) cells stably expressing the CB1 receptor. Pertussis toxin treatment of CHO cells expressing the CB1 receptor attenuated the anandamide-mediated inhibition of adenylate cyclase and unmasked a stimulatory effect of anandamide on adenylate cyclase. The stimulatory component was blocked with LY320135. This compound also blocked WIN 55212–2-mediated inhibition of N-type calcium channels and activation of inwardly rectifying potassium channels in N18 and AtT-20-CB2 cells, respectively. LY320135 is a promising lead compound for the further development of novel, potent and selective cannabinoid antagonists of novel structure.

231 citations

Journal ArticleDOI
TL;DR: A rapid, simple, one-step procedure is described for the separation of cyclic AMP from ATP, ADP, AMP, and P 1 based on selective adsorption of all nucleotides except cyclicAMP on hydrous aluminum oxide.

231 citations

Book ChapterDOI
TL;DR: In this paper, it was shown that α2 receptors may exist in multiple-affinity states reflecting the ability of the α2 binding-site protein to form a complex with additional membrane proteins that themselves are receptors for the physiological substrates guanosine 5'-triphosphate (GTP), Na+, Mg2+, and possibly Ca2+-calmodulin.
Abstract: Publisher Summary Alpha-1 (α1) receptors by and large appear to occur in a single-affinity state with respect to both agonists and antagonists. By comparison, α2 receptors may exist in multiple-affinity states reflecting the ability of the α2 binding-site protein to form a complex with additional membrane proteins that themselves are receptors for the physiological substrates guanosine 5'-triphosphate (GTP), Na+, Mg2+, and possibly Ca2+-calmodulin. Binding studies have also strongly indicated that α2 receptors in most, if not all, tissues are probably coupled in an inhibitory manner to adenylate cyclase, as has been demonstrated in platelets, adipocytes, and NG 108-15 cells. Nothing is known about the mechanisms of regulation of α1 receptors, although both up- and down-regulations of α1 receptor have been demonstrated. In this regard, the ability to label and study α1 receptors on cells in culture would be particularly useful. With regard to α2 receptors, the number of affinity states that exist and their role in terms of the kinetics of α2-receptor coupling to adenylate cyclase are still not clear.

231 citations

Journal ArticleDOI
TL;DR: Southern blot analysis of high molecular weight genomic DNA from rat liver indicated that the genes for the 70- and 82-kDa subunits are different, and Presumably both catalytic subunits must be present and interactive to permit synthesis of cyclic GMP and nitrovasodilator activation.

231 citations

Journal ArticleDOI
TL;DR: The results show that cyclic AMP plays no significant role in the responses of platelets to aggregating agents in the absence of compounds that increase the platelet cyclicAMP concentration above the resting value.
Abstract: Whereas adenosine itself exerted independent stimulatory and inhibitory effects on the adenylate cyclase activity of a platelet particulate fraction at low and high concentrations respectively, 2-substituted and N6-monosubstituted adenosines had stimulatory but greatly decreased inhibitory effects. Deoxyadenosines, on the other hand, had enhanced inhibitory but no stimulatory effects. The most potent inhibitors found were, in order of increasing activity, 9-(tetrahydro-2-furyl)adenine (SQ 22536), 2',5'-dideoxyadenosine and 2'-deoxyadenosine 3'-monophosphate. Kinetic studies on prostaglandin E1-activated adenylate cyclase showed that the inhibition caused by either 2',5'-dideoxyadenosine or compound SQ 22536 was non-competitive with MgATP and that the former compound, at least, showed negative co-operativity; 50% inhibition was observed with 4 micron-2',5'-dideoxyadenosine or 13 micron-SQ 22536. These two compounds also inhibited both the basal and prostaglandin E1-activated adenylate cyclase activities of intact platelets, when these were measured as the increases in cyclic [3H]AMP in platelets that had been labelled with [3H]adenine and were then incubated briefly with papaverine or papaverine and prostaglandin E1. Both compounds, but particularly 2',5'-dideoxyadenosine, markedly decreased the inhibition by prostaglandin E1 of platelet aggregation induced by ADP or [arginine]vasopressin as well as the associated increases in platelet cyclic AMP, so providing further evidence that the effects of prostaglandin E1 on platelet aggregation are mediated by cyclic AMP. 2'-Deoxyadenosine 3'-monophosphate did not affect the inhibition of aggregation by prostaglandin E1, suggesting that the site of action of deoxyadenosine derivatives on adenylate cyclase is intracellular. Neither 2',5'-dideoxyadenosine nor compound SQ 22536 alone induced platelet aggregation. Moreover, neither compound potentiated platelet aggregation or the platelet release reaction when suboptimal concentrations of ADP, [arginine]vasopressin, collagen or arachidonate were added to heparinized or citrated platelet-rich plasma in the absence of prostaglandin E1. These results show that cyclic AMP plays no significant role in the responses of platelets to aggregating agents in the absence of compounds that increase the platelet cyclic AMP concentration above the resting value.

230 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202324
202257
202145
202048
201939
201856