Prostaglandin Receptors: Advances in the Study of EP3 Receptor Signaling

Hatae, Noriyuki; Sugimoto, Yukihiko; Ichikawa, Atsushi

doi:10.1093/oxfordjournals.jbchem.a003165

Cited by 115 publications

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“…In neuronal cells, EP 3 receptor signaling activates Rho through coupling with G 13 , resulting in neuron retraction [10]. In PC12 cells, the EP 3B isoform of the EP 3 receptor is linked to Rho [28].…”

Section: Discussionmentioning

confidence: 99%

“…The EP 1 receptor is a low affinity receptor for PGE 2 that couples to G q to activate phospholipase C [8,9] and raises intracellular calcium. The EP 3 receptor, unlike the other PGE 2 receptors, has multiple isoforms (8 in human and 3 in mice) and couples to multiple small G-proteins, including G(i) (inhibition of adenylate cyclase), G βγ (increase in intracellular Ca +2 ) and G 13 (activation of the small G protein Rho [10]). …”

Section: Introductionmentioning

confidence: 99%

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Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCζ

Scott

Fricke

Fender

et al. 2007

Experimental Cell Research

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Prostaglandins are lipid signaling intermediates released by keratinocytes in response to ultraviolet irradiation (UVR) in the skin. The main prostaglandin released following UVR is PGE 2 , a ligand for 4 related G-protein coupled receptors (EP 1 , EP 2 , EP 3 and EP 4 ). Our previous work established that PGE 2 stimulates melanocyte dendrite formation through activation of the EP 1 and EP 3 receptors. The purpose of the present report is to define the signaling intermediates involved in EP 1 and EP 3 -dependent dendrite formation in human melanocytes. We recently showed that activation of the atypical PKCζ isoform stimulates melanocyte dendricity in response to treatment with lysophosphatidylcholine. We therefore examined the potential contribution of PKCζ activation on EP 1 and EP 3 -dependent dendrite formation in melanocytes. Stimulation of the EP 1 and EP 3 receptors by selective agonists activated PKCζ, and inhibition of PKCζ activation abrogated EP 1 and EP 3 -receptor mediated melanocyte dendricity. Because of the importance of Rho-GTP binding proteins in the regulation of melanocyte dendricity, we also examined the effect of EP 1 and EP 3 receptor activation on Rac and Rho activity. Neither Rac nor Rho was activated upon treatment with EP 1,3 -receptor agonists. We show that melanocytes express only the EP 3A1 isoform, but not the EP 3B receptor isoform, previously associated with Rho activation, consistent with a lack of Rho stimulation by EP 3 agonists. Our data suggest that PKCζ activation plays a predominant role in regulation of PGE 2 -dependent melanocyte dendricity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCζ

Scott

Fricke

Fender

et al. 2007

Experimental Cell Research

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“…For example, activation of presynaptic EP 2 receptors in the hippocampus has been reported to facilitate synaptic glutamate release via increasing cAMP pathway (Sang et al, 2005). However, activation of EP 3 receptors mainly inhibits cAMP generation via Gi coupled mechanisms (Hatae et al, 2002). A large population of EP 3 receptors has been identified in the PAG (Ek et al, 2000;Nakamura et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…EP 1 receptors couple with the Gq-phospholipase C-IP 3 pathway. EP 2 and EP 4 receptors couple with the Gs-adenylyl cyclase-cAMP pathway and activation of those receptors increases cAMP levels (Hatae et al, 2002). Elevated cAMP enhances glutamatergic transmission in the PAG as well as in other brain regions (Huang and Hsu, 2006;Kaneko and Takahashi, 2004;Marabese et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Activation of presynaptic EP 2 receptors in the hippocampus has been reported to facilitate synaptic glutamate release via increasing cAMP pathway (Sang et al, 2005). In contrast, activation of EP 3 receptors mainly inhibits cAMP generation via Gi coupled mechanisms (Hatae et al, 2002). EP 3 is widely distributed in the CNS and plays a role in mediating a number of the physiological functions of PGE 2 (Kumazawa et al, 1993;Oka et al, 1997;Yokotani et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

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Prostaglandin E2 (PGE2) inhibits glutamatergic synaptic transmission in dorsolateral periaqueductal gray (dl-PAG)

Xing

2007

Brain Research

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The purpose of this study was to determine the role of prostaglandin E 2 (PGE 2 ) in modulating neuronal activity of the dorsolateral periaqueductal gray (dl-PAG) through excitatory and inhibitory synaptic inputs. First, whole cell voltage-clamp recording was performed to obtain excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) of the dl-PAG neurons. Our results show that PGE 2 significantly decreased the frequency of miniature EPSCs and amplitude of evoked EPSCs. The effects were mimicked by sulprostone, an agonist to PGE 2 EP 3 receptors. In contrast, PGE 2 had no distinct effect on IPSCs. In addition, spontaneous action potential of the dl-PAG neurons was recorded using whole cell current-clamp methods. PGE 2 significantly attenuated the discharge rate of the dl-PAG neurons. The decreased firing activity was abolished in the presence of glutamate NMDA and non-NMDA receptors antagonists. The results from the current study provide the first evidence indicating that PGE 2 inhibits the neuronal activity of the dl-PAG via selective attenuation of glutamatergic synaptic inputs, likely due to activation of presynaptic EP 3 receptors.

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Antiplatelet Agents

Chackalamannil¹

2010

Burger's Medicinal Chemistry and Drug Discovery

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In addition to their life‐sustaining role in hemostasis and wound healing, platelets play a central role in the pathogenesis of coronary artery, cerebrovascular, and peripheral vascular diseases. Under pathologic conditions such as rupture of an atherosclerotic plaque, the platelet activation mechanism and coagulation mechanism synergize in the formation of an occlusive thrombus leading to ischemic disorders such as acute coronary syndrome and stroke. Antiplatelet agents are the mainstay of pharmacological approach for the treatment of ischemic vascular disorders. Platelets have multiple cell‐surface receptors that, upon activation by specific ligands, trigger a cascade of cellular events resulting in the activation of the integrin glycoprotein (GP) IIb/IIIa receptors. Activated GP IIb/IIIa receptors cross‐link with fibrinogen causing platelet to aggregate. Aggregated platelets get trapped by fibrin meshwork, produced by the proteolysis of fibrinogen by thrombin. Cell‐surface platelet receptors have been the target of antiplatelet therapy. For example, aspirin, the most widely used antiplatelet agent, inhibit the biosynthesis of thromboxane A 2 , the endogenous agonist that activates thromboxane receptors. The ADP antagonists such as clopidogrel and ticlopidine inhibit ADP‐mediated activation of purinergic P2Y 12 receptors. Glycoprotein IIb/IIIa antagonists such as abciximab, eptifibatide, and tirofiban inhibit GP IIb/IIIa receptors, which involve the final common pathway of platelet aggregation. Phosphodiesterase inhibitors are less widely used antiplatelet agents that potentiate intracellular cyclic AMP levels. Promising newer antiplatelet agents such as thrombin receptor antagonists with reduced bleeding liability, third‐generation thienopyridine ADP antagonists with improved potency and reversible ADP antagonists are at advanced stage of development.

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Prostaglandin Receptors: Advances in the Study of EP3 Receptor Signaling

Cited by 115 publications

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Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCζ

Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCζ

Prostaglandin E2 (PGE2) inhibits glutamatergic synaptic transmission in dorsolateral periaqueductal gray (dl-PAG)

Antiplatelet Agents

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