Characterization of prostanoid receptor‐evoked responses in rat sensory neurones

Smith, Jacqueline A.; Amagasu, Shanti; Eglen, Richard M.; Hunter, John C.; Bley, Keith

doi:10.1038/sj.bjp.0701853

Cited by 92 publications

(77 citation statements)

References 68 publications

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“…In nodose neurons, PGD 2 inhibited postspike hyperpolarization, resulting in an increase in the firing frequency (5). Extracellular recording of direct-current potentials indicated that PGD 2 perfusion caused a depolarization response of vagal C fibers (25). However, in another study using in vivo electrophysiological single-unit recording from rat trigeminal ganglion, PGD 2 failed to sensitize meningeal nociceptors (34).…”

Section: Discussionmentioning

confidence: 95%

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Role of prostaglandin D₂ in mast cell activation-induced sensitization of esophageal vagal afferents

Zhang

Grabauskas

Joo

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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S. Role of prostaglandin D 2 in mast cell activationinduced sensitization of esophageal vagal afferents. Am J Physiol Gastrointest Liver Physiol 304: G908 -G916, 2013. First published March 7, 2013 doi:10.1152/ajpgi.00448.2012.-Sensitization of esophageal afferents plays an important role in esophageal nociception, but the mechanism is less clear. Our previous studies demonstrated that mast cell (MC) activation releases the preformed mediators histamine and tryptase, which play important roles in sensitization of esophageal vagal nociceptive C fibers. PGD 2 is a lipid mediator released by activated MCs. Whether PGD2 plays a role in this sensitization process has yet to be determined. Expression of the PGD 2 DP1 and DP2 receptors in nodose ganglion neurons was determined by immunofluorescence staining, Western blotting, and RT-PCR. Extracellular recordings were performed in ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal distension were compared before and after perfusion of PGD 2, DP1 and DP2 receptor agonists, and MC activation, with or without pretreatment with antagonists. The effect of PGD2 on 1,1=-dioctadecyl-3,3,3=,3=-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal nodose neurons was determined by patch-clamp recording. Our results demonstrate that DP1 and DP2 receptor mRNA and protein were expressed mainly in small-and medium-diameter neurons in nodose ganglia. PGD2 significantly increased esophageal distension-evoked action potential discharges in esophageal nodose C fibers. The DP1 receptor agonist BW 245C mimicked this effect. PGD2 directly sensitized DiI-labeled esophageal nodose neurons by decreasing the action potential threshold. Pretreatment with the DP1 receptor antagonist BW A868C significantly inhibited PGD2 perfusion-or MC activation-induced increases in esophageal distensionevoked action potential discharges in esophageal nodose C fibers. In conclusion, PGD2 plays an important role in MC activation-induced sensitization of esophageal nodose C fibers. This adds a novel mechanism of visceral afferent sensitization.

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Section: Discussionmentioning

confidence: 95%

“…Its effect on peripheral afferents is less clear. In cultured DRG neurons, PGD 2 evoked an accumulation of cAMP (25) and increased the amplitude of TTX-resistant Na ϩ currents via the DP 1 receptor (7). In nodose neurons, PGD 2 inhibited postspike hyperpolarization, resulting in an increase in the firing frequency (5).…”

Section: Discussionmentioning

confidence: 99%

Role of prostaglandin D₂ in mast cell activation-induced sensitization of esophageal vagal afferents

Zhang

Grabauskas

Joo

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Given that NP-1 does not have a known signaling function, we next examined other signaling pathways that could be responsible for mediating VEGF-dependent inhibition of DRG growth cone collapse. Prostaglandins exert direct effects on sensory neurons via specific EP and IP receptors (37)(38)(39)(40) and also mediate biological functions of VEGF (12,16). The role of prostanoids in regulating neurotrophic or growth cone activity has not been examined previously, however (Fig.…”

Section: Resultsmentioning

confidence: 99%

Anti-chemorepulsive Effects of Vascular Endothelial Growth Factor and Placental Growth Factor-2 in Dorsal Root Ganglion Neurons Are Mediated via Neuropilin-1 and Cyclooxygenase-derived Prostanoid Production

Cheng¹,

Jia

Löhr

et al. 2004

Journal of Biological Chemistry

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Vascular endothelial growth factor (VEGF) displays neurotrophic and neuroprotective activities, but the mechanisms underlying these effects have not been defined. Neuropilin-1 (NP-1) is a receptor for VEGF 165 and placental growth factor-2 (PlGF-2), but the role of NP-1 in VEGF-dependent neurotrophic actions is unclear. Dorsal root ganglion (DRG) neurons expressed high levels of NP-1 mRNA and protein, much lower levels of KDR, and no detectable Flt-1. VEGF 165 and PlGF-2 promoted DRG growth cone formation with an effect similar to that of nerve growth factor, whereas the Flt-1-specific ligand, PlGF-1, and the KDR/Flt-4 ligand, VEGF-D, had no effect. The chemorepellent NP-1 ligand, semaphorin 3A, antagonized the response to VEGF and PlGF-2. The specific KDR inhibitor, SU5614, did not affect the anti-chemorepellent effects of VEGF and PlGF-2, whereas a novel, specific antagonist of VEGF binding to NP-1, called EG3287, prevented inhibition of growth cone collapse. VEGF stimulated prostacyclin and prostaglandin E 2 production in DRG cultures that was blocked by inhibitors of cyclooxygenases; the anti-chemorepellent activities of VEGF and PlGF-2 were abrogated by cyclooxygenase inhibitors, and a variety of prostacyclin analogues and prostaglandins strikingly inhibited growth cone collapse. These findings support a specific role for NP-1 in mediating neurotrophic actions of VEGF family members and also identify a novel role for prostanoids in the inhibition of neuronal chemorepulsion.

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“…Thus, the effect elicited by 1 M butaprost is not restricted to the EP2 receptor and may be mediated by activation of other prostanoid receptors. In addition, butaprost at micromolar concentrations binds to the mouse IP receptor (57), and IP receptor agonists increase icAMP content in sensory neurons (18,62). Since IP receptor expression was not affected by antisense treatment to EP3C and EP4, there are sufficient IP receptors available to potentially mediate the actions of butaprost.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin Receptor Subtypes, EP3C and EP4, Mediate the Prostaglandin E2-induced cAMP Production and Sensitization of Sensory Neurons

Southall¹,

Vasko

2001

Journal of Biological Chemistry

168

150

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Although a number of prostaglandin E 2 (PGE 2 ) receptor subtypes have been cloned, limited studies have been performed to elucidate subtypes that subserve specific actions of this eicosanoid, in part because of a paucity of selective receptor antagonists. Using reverse transcription-polymerase chain reaction (PCR) and antisense oligonucleotides, we examined which prostaglandin E 2 receptor (EP receptor) subtypes are expressed in sensory neurons and which mediate the PGE 2 -induced increase in cAMP production and augmentation of peptide release. Reverse transcription-PCR of cDNA isolated from rat sensory neurons grown in culture revealed PCR products for the EP1, EP2, EP3C, and EP4 receptor subtypes but not the EP3A or EP3B. Preexposing neuronal cultures for 48 h to antisense oligonucleotides of EP3C and EP4 mRNA diminished expression of the respective receptors by ϳ80%, abolished the PGE 2 -stimulated production of cAMP, and blocked the ability of PGE 2 to augment release of immunoreactive substance P and calcitonin gene-related peptide. Pretreating with individual antisense against the EP2, EP3C, or EP4 receptors or combinations of missense oligonucleotides had no effect on PGE 2 -induced activity. Treatment with antisense to EP3C and EP4 receptor subtypes did not alter the ability of forskolin to increase cAMP or enhance peptide release. These results demonstrate that sensory neurons are capable of expressing multiple EP receptor subtypes but that only the EP3C and EP4 receptors mediate PGE 2 -induced sensitization of sensory neurons. Prostaglandin E 2 receptors (EP receptors)1 have been classified into four general subtypes, EP1, EP2, EP3, and EP4, based on cloning and pharmacological manipulations (1, 2). These receptors are G-protein-coupled, and binding of agonists results in activation of various transduction cascades depending on the receptor subtype activated and the cells being studied. Activation of the EP1 receptor in kidney tubule cells increases the concentration of intracellular calcium, phosphoinositol turnover, and PKC activity (3, 4). EP2 and EP4 receptors are coupled through G s (1) to increase intracellular cAMP in a number of preparations (5-8). The EP3 receptor undergoes post-transcriptional RNA splicing to produce multiple EP3 isoforms, and activation of these splice variants can increase calcium mobilization or either stimulate or inhibit cAMP production (9 -11). Because subtypes of the EP receptor can be linked to different transduction cascades in different types of cells, it is critical to determine which receptors and receptorassociated signal transduction pathways are responsible for specific physiological actions of E-series prostaglandins.Although PGE 2 has a number of diverse physiological actions (12), its role in pain and inflammation is of primary importance. Indeed, both the analgesic and the anti-inflammatory actions of the nonsteroidal anti-inflammatory drugs are attributed to their ability to inhibit prostaglandin synthesis (13). In addition, PGE 2 is produced at sites of ...

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Characterization of prostanoid receptor‐evoked responses in rat sensory neurones

Cited by 92 publications

References 68 publications

Role of prostaglandin D₂ in mast cell activation-induced sensitization of esophageal vagal afferents

Role of prostaglandin D₂ in mast cell activation-induced sensitization of esophageal vagal afferents

Anti-chemorepulsive Effects of Vascular Endothelial Growth Factor and Placental Growth Factor-2 in Dorsal Root Ganglion Neurons Are Mediated via Neuropilin-1 and Cyclooxygenase-derived Prostanoid Production

Prostaglandin Receptor Subtypes, EP3C and EP4, Mediate the Prostaglandin E2-induced cAMP Production and Sensitization of Sensory Neurons

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Characterization of prostanoid receptor‐evoked responses in rat sensory neurones

Cited by 92 publications

References 68 publications

Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents

Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents

Anti-chemorepulsive Effects of Vascular Endothelial Growth Factor and Placental Growth Factor-2 in Dorsal Root Ganglion Neurons Are Mediated via Neuropilin-1 and Cyclooxygenase-derived Prostanoid Production

Prostaglandin Receptor Subtypes, EP3C and EP4, Mediate the Prostaglandin E2-induced cAMP Production and Sensitization of Sensory Neurons

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Role of prostaglandin D₂ in mast cell activation-induced sensitization of esophageal vagal afferents

Role of prostaglandin D₂ in mast cell activation-induced sensitization of esophageal vagal afferents