Functional role of prostacyclin receptor in rat dorsal root ganglion neurons

Nakae, Koichi; Hayashi, Fumio; Hayashi, Mayumi; Yamamoto, Norio; Iino, Takashi; Gupta, Jang B.

doi:10.1016/j.neulet.2005.06.058

Cited by 25 publications

(24 citation statements)

References 25 publications

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“…Regarding signal transduction mechanisms of prostanoids in sensory neurons, both PGI 2 analogs and PGE 2 stimulated cAMP accumulation in cultured rat DRG neurons (523,526,662,668,776). The PGE 2 -induced cAMP accumulation was mediated by EP 3C and EP 4 receptors (526,668,776).…”

Section: Prostanoid Receptors and Their Intracellular Signaling Mechamentioning

confidence: 96%

“…215) but not from isolated mouse sciatic nerve axons (29,200,348). Bradykinin caused a release of both SP and CGRP from cultured DRG neurons (42,177,523,524,663,687,710,742), and this response was diminished by inhibition of PKC (42), block of N-, but not L-or P-, type voltage-gated Ca 2ϩ channels (177). However, this synaptic N type of voltagegated Ca 2ϩ channels is not involved in depolarization-induced neuropeptide release from peripheral nerve fibers where low-threshold T and also L-type channels govern the exocytosis of CGRP that entirely depends on extracellular Ca 2ϩ (669).…”

Section: Plc Pkc and Intracellular Ca 2ϩ In Bradykinin Receptor Sigmentioning

confidence: 99%

“…With regard to the receptor subtypes mediating the sensory actions of prostaglandins, EP 1 , EP 2 , EP 3B , EP 3C , EP 4 , DP 1 , DP 2 , and IP receptors are all possible candidates since the mRNAs and/or proteins of these subtypes (but not that of EP 3A ) were revealed in mouse and/or rat DRG neurons (25,156,167,180,433,447,523,547,668,683). Later, EP 3A receptors were cloned from dog DRG neurons and shown to couple with G i and G q protein (385).…”

Section: Prostanoid Receptors and Their Intracellular Signaling Mechamentioning

confidence: 99%

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Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Pethő

Reeh

2012

Physiological Reviews

244

200

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Peripheral mediators can contribute to the development and maintenance of inflammatory and neuropathic pain and its concomitants (hyperalgesia and allodynia) via two mechanisms. Activation or excitation by these substances of nociceptive nerve endings or fibers implicates generation of action potentials which then travel to the central nervous system and may induce pain sensation. Sensitization of nociceptors refers to their increased responsiveness to either thermal, mechanical, or chemical stimuli that may be translated to corresponding hyperalgesias. This review aims to give an account of the excitatory and sensitizing actions of inflammatory mediators including bradykinin, prostaglandins, thromboxanes, leukotrienes, platelet-activating factor, and nitric oxide on nociceptive primary afferent neurons. Manifestations, receptor molecules, and intracellular signaling mechanisms of the effects of these mediators are discussed in detail. With regard to signaling, most data reported have been obtained from transfected nonneuronal cells and somata of cultured sensory neurons as these structures are more accessible to direct study of sensory and signal transduction. The peripheral processes of sensory neurons, where painful stimuli actually affect the nociceptors in vivo, show marked differences with respect to biophysics, ultrastructure, and equipment with receptors and ion channels compared with cellular models. Therefore, an effort was made to highlight signaling mechanisms for which supporting data from molecular, cellular, and behavioral models are consistent with findings that reflect properties of peripheral nociceptive nerve endings. Identified molecular elements of these signaling pathways may serve as validated targets for development of novel types of analgesic drugs.

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Section: Prostanoid Receptors and Their Intracellular Signaling Mechamentioning

confidence: 96%

Section: Plc Pkc and Intracellular Ca 2ϩ In Bradykinin Receptor Sigmentioning

confidence: 99%

Section: Prostanoid Receptors and Their Intracellular Signaling Mechamentioning

confidence: 99%

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Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Pethő

Reeh

2012

Physiological Reviews

244

200

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“…In DRG neuron, the release of excitatory neuropeptide substance P is induced by capsaicin, bradykinin and ATP [10], and capsaicin-induced currents are enhanced by the activation of PKC [11]. Moreover, it was reported that PKC signaling is involved in the mechanism of sensitization and also that TRPV1 is directly phosphorylated by PKC [15].…”

Section: Discussion and Summurymentioning

confidence: 99%

“…The Effect of GlcNAc-TA and PMA on Substance P Release from DRG Neurons Capsaicin is a ligand of transient receptor potential vanilloid 1 (TRPV1) and induces the release of substance P from DRG neurons [10]. It is reported that PKC regulates the currents of DRG neurons induced by capsaicin in rats [11].…”

Section: Biological Activitiesmentioning

confidence: 99%

A New Teleocidin Analog from Streptomyces sp. MM216-87F4 Induces Substance P Release from Rat Dorsal Root Ganglion Neurons

et al. 2006

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A new teleocidin analog was isolated from the fermentation medium of Streptomyces sp. MM216-87F4 and its structure was elucidated as 14-O-(Nacetylglucosaminyl) teleocidin A (GlcNAc-TA). GlcNAc-TA induces the translocation of protein kinases Ca and q fused with enhanced green fluorescent protein (PKCa -EGFP and PKCq -EGFP) to the plasma membrane in stable transfectants, and reduces intracellular calcium mobilization induced by agonists of G-protein coupled receptors in various cell lines without causing irritation of the mouse ear. Further, GlcNAc-TA sensitizes the release of excitatory neuropeptides substance P induced by capsaicin from primary-cultured dorsal root ganglion (DRG) neurons of the rat and GlcNAc-TA alone also triggers substance P release in a dose-dependent manner. This study provides the first observation that a teleocidin analog without a free hydroxyl group at C-14 acts as a PKC activator and directly induces the release of excitatory neuropeptide.

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Asymmetric Synthesis of 3‐Oxa‐15‐deoxy‐16‐(m‐tolyl)‐17,18,19,20‐tetranorisocarbacyclin and Its Neuroprotective Analogue 15‐Deoxy‐16‐(m‐tolyl)‐17,18,19,20‐tetranorisocarbacyclin Based on the Conjugate Addition–Azoalkene–Asymmetric Olefination Strategy

Sande

Gais

2007

Chemistry A European J

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A fully stereocontrolled synthesis of 3-oxa-15-deoxy-16-(m-tolyl)-17,18,19,20-tetranorisocarbacyclin (3-oxa-15-deoxy-TIC, 7 b) and a formal one of 15-deoxy-16-(m-tolyl)-17,18,19,20-tetranorisocarbacyclin (15-deoxy-TIC, 7 a) are described. 15-Deoxy-TIC is specific for the neuronal prostacyclin receptor (IP2) and exhibits neuroprotective activities, and the new 3-oxa-15-deoxy-TIC is expected to be metabolically more stable than 15-deoxy-TIC. The syntheses of 7 a and 7 b are based on the convergent conjugate addition-azoalkene-asymmetric olefination strategy. Key building blocks are the readily available bicyclic azoalkene 14 and the alkenylcopper derivative 15. The stereoselective conjugate addition of 15 to 14 gave hydrazone 13, which was stereoselectively converted to the bicyclic ketone 11. The key steps for the construction of the alpha side chain of 7 a and 7 b and the regioselective introduction of the endocyclic Delta6,6a double bond are: 1) a highly selective asymmetric olefination of ketone 11 with the chiral Horner-Wadsworth-Emmons reagent 28 and 2) a regioselective deconjugation of the alpha,beta-unsaturated ester (E)-10 with the chiral lithium amide 29, which gave the beta,gamma-unsaturated ester anti-9 with high selectivity. The homoallylic alcohol 8 served at a late stage as the joint intermediate in the syntheses of 7 a and 7 b. While an etherification of 8 furnished, after hydrolysis and deprotection, 3-oxa-15-deoxy-TIC, its alkylation afforded alcohol 37, the known precursor for the synthesis of 15-deoxy-TIC.

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Functional role of prostacyclin receptor in rat dorsal root ganglion neurons

Cited by 25 publications

References 25 publications

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

A New Teleocidin Analog from Streptomyces sp. MM216-87F4 Induces Substance P Release from Rat Dorsal Root Ganglion Neurons

Asymmetric Synthesis of 3‐Oxa‐15‐deoxy‐16‐(m‐tolyl)‐17,18,19,20‐tetranorisocarbacyclin and Its Neuroprotective Analogue 15‐Deoxy‐16‐(m‐tolyl)‐17,18,19,20‐tetranorisocarbacyclin Based on the Conjugate Addition–Azoalkene–Asymmetric Olefination Strategy

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