The oral administration of retinoic acid enhances nociceptive withdrawal reflexes in rats with soft-tissue inflammation

Romero‐Sandoval, E. Alfonso; Alique, Matilde; Moreno‐Manzano, Victoria; Molina, Carlos; Lucio, F.; Herrero, Juan F.

doi:10.1007/s00011-004-1261-5

Cited by 21 publications

(35 citation statements)

References 34 publications

(44 reference statements)

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“…2 C, right panel) thus suggesting that activation of RAR or RXR leads to increased COX-2 mRNA expression in rat MC. We have previously shown that treatment with ATRA results in an increased COX-2 expression in the rat spinal cord [25] . However, ATRA did not induce COX-2 in phorbol 12-myristate 13-acetate-differentiated U937 cells [31] whereas it suppressed COX-2 transcription in human mammary epithelial cells [36] .…”

Section: Discussionmentioning

confidence: 99%

“…Cell proteins (30-40 g) were run in a 8-10% SDS-polyacrylamide gel, transferred onto a nitrocellulose membrane (Trans-Blot Transfer Medium, Bio-Rad, Richmond, Calif., USA) and incubated overnight at 4 ° C with antibodies recognizing specifically COX-1 (Santa Cruz Biotechnology, Santa Cruz, Calif., and Cayman Chemical, Ann Arbor, Mich., USA) and COX-2 (Santa Cruz Biotechnology) as previously described [25] . This incubation, in which antibodies were used at a dilution 1: 1,000, was followed by a second incubation with a peroxidase-conjugated secondary antibody (1: 5,000 dilution) and immunoreactive products were detected by chemiluminescence using the ECL Western Blotting Detection Reagents (Amersham Biosciences, Little Chalfont, UK) following the protocol provided by the manufacturer.…”

Section: Western Blot Analysismentioning

confidence: 99%

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Upregulation of Cyclooxygenases by Retinoic Acid in Rat Mesangial Cells

Alique

Lucio-Cazaña

et al. 2006

Pharmacology

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All-trans retinoic acid (ATRA) increases the expression of COX-1 and COX-2 and the production of PGE₂, a prostaglandin with anti-inflammatory effects in human mesangial cells (MC). COX-2 increased through a transcriptional mechanism independent of retinoic acid receptors (RAR) and retinoid X receptors (RXR) and dependent on extracellular regulated kinase-1/2 (ERK1/2), that became phosphorylated 5 min after ATRA addition. Here, in rat MC, ATRA also upregulated COX isoenzymes and PGE₂ production, but not in the same way as in human MC: (1) PGE₂ production increased only slightly; (2) RAR and RXR were involved in the transcriptional upregulation of COX-2 by ATRA since the RAR-pan-antagonist AGN193109 or the RXR-pan-antagonist HX531 abolished the induction of COX-2 mRNA whereas the RAR-pan-agonist TTNPB or the RXR-pan-agonist AGN194204 induced expression of COX-2, and (3) ERK1/2 phosphorylation, though important for COX-2 upregulation, took more than 1 h. Therefore the regulation of COX by ATRA exhibits striking differences between human and rat MC.

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Section: Discussionmentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

Upregulation of Cyclooxygenases by Retinoic Acid in Rat Mesangial Cells

Alique

Lucio-Cazaña

et al. 2006

Pharmacology

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“…Oral or intrathecal application of vitamin A derivatives also was shown to increase nocifensive responses in rodents with or without tissue inflammation (14,15). However, the cellular and molecular basis of retinoid signaling in the pain pathway had not been explored.…”

Section: Discussionmentioning

confidence: 99%

“…Retinoid-elicited irritation has become a major clinical issue and is the main reason that many patients discontinue retinoid treatment (9)(10)(11)(12)(13). Animal studies have shown that oral or intrathecal application of ATRA induced nociceptive behavioral effects, suggesting a sensitization of nociceptive pathways by retinoids (14,15). However, the molecular mechanisms mediating retinoid-induced sensory hypersensitivity are undetermined, and highly effective treatment options for these side effects are lacking.…”

Section: Introductionmentioning

confidence: 99%

“…Left hind paws of mice were injected intraplantarly with 10 μl vehicle (saline + 1% DMSO + 0.1% Tween 80) with or without chemicals. For assessment of thermal nociception, left hind paw withdrawal latencies were measured before (0 minutes) and 15,30,60,90, and 120 minutes after injections. The infrared intensity was adjusted to obtain basal paw withdrawal latencies of 10 to 15 seconds.…”

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confidence: 99%

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Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity

et al. 2013

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Retinoids are structurally related derivatives of vitamin A and are required for normal vision as well as cell proliferation and differentiation. Clinically, retinoids are effective in treating many skin disorders and cancers. Application of retinoids evokes substantial irritating side effects, including pain and inflammation; however, the precise mechanisms accounting for the sensory hypersensitivity are not understood. Here we show that both naturally occurring and synthetic retinoids activate recombinant or native transient receptor potential channel vanilloid subtype 1 (TRPV1), an irritant receptor for capsaicin, the pungent ingredient of chili peppers. In vivo, retinoids produced pain-related behaviors that were either eliminated or significantly reduced by genetic or pharmacological inhibition of TRPV1 function. These findings identify TRPV1 as an ionotropic receptor for retinoids and provide cellular and molecular insights into retinoid-evoked hypersensitivity. These findings also suggest that selective TRPV1 antagonists are potential therapeutic drugs for treating retinoid-induced sensory hypersensitivity.

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The regulators of G protein signaling RGS16 and RGS18 inhibit protease‐activated receptor 2/Gi/o signaling through distinct interactions with Gα in live cells

2018

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Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor (GPCR) activated by endogenous proteases, in particular, trypsin. Although regulators of G protein signaling (RGS) are known to inhibit GPCR/Gα-mediated signaling, their specific effects on PAR2 are poorly understood at present. Here, we use a bioluminescence resonance energy transfer technique to investigate whether RGS16 and RGS18 bind PAR2 in live cells to regulate PAR2/Gα -mediated signaling. Notably, we find that RGS16 binds to PAR2 in the presence of Gα while RGS18 does not interact with PAR2, regardless of the presence of Gα. Both RGS16 and RGS18 inhibit PAR2/Gα -mediated signaling. To our knowledge, the current study is the first to highlight the effects of RGS proteins on PAR2-mediated signaling.

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The oral administration of retinoic acid enhances nociceptive withdrawal reflexes in rats with soft-tissue inflammation

Abstract: A clear relationship between the oral administration of ATRA and an enhancement of the nociceptive withdrawal reflexes was observed in rats. This relationship was associated with an increment of the expression of the COX-2 enzyme.

Cited by 21 publications

References 34 publications

Upregulation of Cyclooxygenases by Retinoic Acid in Rat Mesangial Cells

Upregulation of Cyclooxygenases by Retinoic Acid in Rat Mesangial Cells

Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity

The regulators of G protein signaling RGS16 and RGS18 inhibit protease‐activated receptor 2/Gi/o signaling through distinct interactions with Gα in live cells

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