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Inflammopharmacology

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15.07.2019 | Original Article

The investigation of possible roles of central 5-HT₇ receptors in antipyretic effect mechanism of paracetamol in LPS-induced hyperthermia model of mice

verfasst von: Duygu Kose, Elif Cadirci, Zekai Halici, Busra Sirin, Busra Dincer

Erschienen in: Inflammopharmacology | Ausgabe 6/2019

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Abstract

Aim

This study aimed to investigate the role of the 5-HT₇ receptor in fever mechanisms and its possible effect on the antipyretic mechanism of paracetamol.

Materials and methods

The study consisted of eight experimental groups and one control group. Group I: healthy, II: LPS, III: LPS + PARA, IV: LPS + AGO, V: LPS + ANTA, VI: LPS + AGO + ANTA, VII: LPS + AGO + PARA, VIII: LPS + ANTA + PARA, and IX: LPS + AGO + ANTA + PARA. Rectal temperatures were measured with a rectal thermometer. At the end of the experiment, tissues were examined molecularly. Real-time PCR mRNA expression analyses were performed for the 5-HT7 receptor, IL-6, and TNF-α in hypothalamus tissue.

Results

The mean differences in rectal temperature increased in the LPS, LPS + ANTA, and LPS + AGO + ANTA groups when compared to the healthy group and decreased in the LPS + PARA, LPS + AGO, LPS + AGO + PARA, and LPS + AGO + ANTA + PARA groups when compared to the healthy group. The IL-6 and TNF-α mRNA expression increased in the LPS, LPS + ANTA, and LPS + AGO + ANTA groups when compared to the healthy group in the 2nd and 4th hours. The IL-6 and TNF-α expression decreased in the LPS + PARA, LPS + AGO, LPS + AGO + PARA, and LPS + AGO + ANTA + PARA groups when compared to the LPS group in the 2nd and 4th hours. The 5-HT₇ receptor mRNA expression increased in the LPS group when compared to the healthy group in the 2nd hour. The 5-HT₇ receptor mRNA expression decreased in the LPS + AGO and LPS + AGO + PARA groups when compared to the LPS group in the 2nd hour. The 5-HT₇ receptor mRNA expression increased the in LPS + ANTA and LPS + ANTA + PARA groups when compared to the LPS group in the 2nd hour.

Conclusion

The 5-HT₇ receptor is a potential defense mechanism in stopping fever and the antipyretic property of paracetamol is not due to the 5-HT₇ receptor.

Albayrak A, Halici Z, Cadirci E, Polat B, Karakus E, Bayir Y, Unal D, Atasoy M, Dogrul A (2013) Inflammation and peripheral 5-HT7 receptors: the role of 5-HT7 receptors in carrageenan induced inflammation in rats. Eur J Pharmacol 715:270–279PubMed

Bjorkman R, Hallman KM, Hedner J, Hedner T, Henning M (1994) Acetaminophen blocks spinal hyperalgesia induced by NMDA and substance P. Pain 57:259–264PubMed

Bonaventure P, Nepomuceno D, Hein L, Sutcliffe JG, Lovenberg T, Hedlund PB (2004) Radioligand binding analysis of knockout mice reveals 5-hydroxytryptamine(7) receptor distribution and uncovers 8-hydroxy-2-(di-n-propylamino)tetralin interaction with alpha(2) adrenergic receptors. Neuroscience 124:901–911PubMed

Brenchat A, Rocasalbas M, Zamanillo D, Hamon M, Vela JM, Romero L (2012) Assessment of 5-HT(7) receptor agonists selectivity using nociceptive and thermoregulation tests in knockout versus wild-type mice. Adv Pharmacol Sci 2012:312041PubMedPubMedCentral

Cadirci E, Halici Z, Bayir Y, Albayrak A, Karakus E, Polat B, Unal D, Atamanalp SS, Aksak S, Gundogdu C (2013) Peripheral 5-HT7 receptors as a new target for prevention of lung injury and mortality in septic rats. Immunobiology 218:1271–1283PubMed

Cayir A, Ugan RA, Albayrak A, Kose D, Akpinar E, Cayir Y, Atmaca HT, Bayraktutan Z, Kara M (2015) The lung endothelin system: a potent therapeutic target with bosentan for the amelioration of lung alterations in a rat model of diabetes mellitus. J Endocrinol Investig 38:987–998

Celik M, Kose A, Kose D, Karakus E, Akpinar E, Calik M, Dostbil A, Calikoglu C, Aksoy M, Ozel L (2015) The double-edged sword: effects of pregabalin on experimentally induced sciatic nerve transection and crush injury in rats. Int J Neurosci 125:845–854PubMed

Faure C, Mnie-Filali O, Scarna H, Debonnel G, Haddjeri N (2006) Effects of the 5-HT7 receptor antagonist SB-269970 on rat hormonal and temperature responses to the 5-HT1A/7 receptor agonist 8-OH-DPAT. Neurosci Lett 404:122–126PubMed

Fukushima A, Sekiguchi W, Mamada K, Tohma Y, Ono H (2017) Serotonergic system does not contribute to the hypothermic action of acetaminophen. Biol Pharm Bull 40:227–233PubMed

Graham GG, Scott KF (2005) Mechanism of action of paracetamol. Am J Ther 12:46–55PubMed

Guscott MR, Egan E, Cook GP, Stanton JA, Beer MS, Rosahl TW, Hartmann S, Kulagowski J, McAllister G, Fone KC, Hutson PH (2003) The hypothermic effect of 5-CT in mice is mediated through the 5-HT7 receptor. Neuropharmacology 44:1031–1037PubMed

Hannon J, Hoyer D (2008) Molecular biology of 5-HT receptors. Behav Brain Res 195:198–213PubMed

Hansen HD, Herth MM, Ettrup A, Andersen VL, Lehel S, Dyssegaard A, Kristensen JL, Knudsen GM (2014) Radiosynthesis and in vivo evaluation of novel radioligands for PET imaging of cerebral 5-HT7 receptors. J Nucl Med 55:640–646PubMed

Hedlund PB, Kelly L, Mazur C, Lovenberg T, Sutcliffe JG, Bonaventure P (2004) 8-OH-DPAT acts on both 5-HT1A and 5-HT7 receptors to induce hypothermia in rodents. Eur J Pharmacol 487:125–132PubMed

Henker R, Carlson KK (2007) Fever: applying research to bedside practice. AACN Adv Crit Care 18:76–87PubMed

Iwasa T, Matsuzaki T, Kinouchi R, Gereltsetseg G, Murakami M, Munkhzaya M, Altankhuu T, Kuwahara A, Yasui T, Irahara M (2014) Changes in central and peripheral inflammatory responses to lipopolysaccharide in ovariectomized female rats. Cytokine 65:65–73PubMed

Kao CH, Kao TY, Huang WT, Lin MT (2007) Lipopolysaccharide- and glutamate-induced hypothalamic hydroxyl radical elevation and fever can be suppressed by N-methyl-d-aspartate-receptor antagonists. J Pharmacol Sci 104:130–136PubMed

Karaman A, Diyarbakir B, Durur-Subasi I, Kose D, Ozbek-Bilgin A, Topcu A, Gundogdu C, Durur-Karakaya A, Bayraktutan Z, Alper F (2016) A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine. Br J Radiol 89:20150716PubMedPubMedCentral

Li S, Dou W, Tang Y, Goorha S, Ballou LR, Blatteis CM (2008) Acetaminophen: antipyretic or hypothermic in mice? In either case, PGHS-1b (COX-3) is irrelevant. Prostaglandins Other Lipid Mediat 85:89–99PubMed

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408PubMed

Mallet C, Daulhac L, Bonnefont J, Ledent C, Etienne M, Chapuy E, Libert F, Eschalier A (2008) Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia. Pain 139:190–200PubMed

Naumenko VS, Kondaurova EM, Popova NK (2011) On the role of brain 5-HT7 receptor in the mechanism of hypothermia: comparison with hypothermia mediated via 5-HT1A and 5-HT3 receptor. Neuropharmacology 61:1360–1365PubMed

Ogimoto K, Harris MK Jr, Wisse BE (2006) MyD88 is a key mediator of anorexia, but not weight loss, induced by lipopolysaccharide and interleukin-1 beta. Endocrinology 147:4445–4453PubMed

Oka T, Oka K, Kobayashi T, Sugimoto Y, Ichikawa A, Ushikubi F, Narumiya S, Saper CB (2003) Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP1 and EP3 receptors. J Physiol 551:945–954PubMedPubMedCentral

Ouellet M, Percival MD (2001) Mechanism of acetaminophen inhibition of cyclooxygenase isoforms. Arch Biochem Biophys 387:273–280PubMed

Palabiyik SS, Karakus E, Akpinar E, Halici Z, Bayir Y, Yayla M, Kose D (2016) The role of urotensin receptors in the paracetamol-induced hepatotoxicity model in mice: ameliorative potential of urotensin II antagonist. Basic Clin Pharmacol Toxicol 118:150–159PubMed

Pickering G, Esteve V, Loriot MA, Eschalier A, Dubray C (2008) Acetaminophen reinforces descending inhibitory pain pathways. Clin Pharmacol Ther 84:47–51PubMed

Raffa RB, Codd EE (1996) Lack of binding of acetaminophen to 5-HT receptor or uptake sites (or eleven other binding/uptake assays). Life Sci 59:PL37–PL40PubMed

Raffa RB, Walker EA, Sterious SN (2004) Opioid receptors and acetaminophen (paracetamol). Eur J Pharmacol 503:209–210PubMed

Roca-Vinardell A, Ortega-Alvaro A, Gibert-Rahola J, Mico JA (2003) The role of 5-HT1A/B autoreceptors in the antinociceptive effect of systemic administration of acetaminophen. Anesthesiology 98:741–747PubMed

Ruud LE, Wilhelms DB, Eskilsson A, Vasilache AM, Elander L, Engblom D, Blomqvist A (2013) Acetaminophen reduces lipopolysaccharide-induced fever by inhibiting cyclooxygenase-2. Neuropharmacology 71:124–129

Savignac HM, Couch Y, Stratford M, Bannerman DM, Tzortzis G, Anthony DC, Burnet PWJ (2016) Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-beta levels in male mice. Brain Behav Immun 52:120–131PubMedPubMedCentral

Schneiders J, Fuchs F, Damm J, Herden C, Gerstberger R, Soares DM, Roth J, Rummel C (2015) The transcription factor nuclear factor interleukin 6 mediates pro- and anti-inflammatory responses during LPS-induced systemic inflammation in mice. Brain Behav Immun 48:147–164PubMed

Siegert R, Philipp-Dormston WK, Radsak K, Menzel H (1976) Mechanism of fever induction in rabbits. Infect Immun 14:1130–1137PubMedPubMedCentral

Sirko S, Bishai I, Coceani F (1989) Prostaglandin formation in the hypothalamus in vivo: effect of pyrogens. Am J Physiol 256:R616–R624PubMed

Tatar A, Yayla M, Kose D, Halici Z, Yoruk O, Polat E (2016) The role of endothelin-1 and endothelin receptor antagonists in allergic rhinitis inflammation: ovalbumin-induced rat model. Rhinology 54:266–272PubMed

Thomas DR, Hagan JJ (2004) 5-HT7 receptors. Curr Drug Targets CNS Neurol Disord 3:81–90PubMed

Tollner B, Roth J, Storr B, Martin D, Voigt K, Zeisberger E (2000) The role of tumor necrosis factor (TNF) in the febrile and metabolic responses of rats to intraperitoneal injection of a high dose of lipopolysaccharide. Pflugers Arch 440:925–932PubMed

Tzirogiannis KN, Kourentzi KT, Zyga S, Papalimneou V, Tsironi M, Grypioti AD, Protopsaltis I, Panidis D, Panoutsopoulos GI (2014) Effect of 5-HT7 receptor blockade on liver regeneration after 60–70% partial hepatectomy. BMC Gastroenterol 14:201PubMedPubMedCentral

Ueno R, Narumiya S, Ogorochi T, Nakayama T, Ishikawa Y, Hayaishi O (1982) Role of prostaglandin D2 in the hypothermia of rats caused by bacterial lipopolysaccharide. Proc Natl Acad Sci USA 79:6093–6097PubMedPubMedCentral

Varnas K, Thomas DR, Tupala E, Tiihonen J, Hall H (2004) Distribution of 5-HT7 receptors in the human brain: a preliminary autoradiographic study using [3H]SB-269970. Neurosci Lett 367:313–316PubMed

Vasefi MS, Yang K, Li J, Kruk JS, Heikkila JJ, Jackson MF, Macdonald JF, Beazely MA (2013) Acute 5-HT7 receptor activation increases NMDA-evoked currents and differentially alters NMDA receptor subunit phosphorylation and trafficking in hippocampal neurons. Mol Brain 6:24PubMedPubMedCentral

Yayla M, Halici Z, Kose D, Tatar A, Sitki Gozeler M (2017) 5-HT7 receptors are over-expressed in patients with nasal polyps. Ear Nose Throat J 96:E14–E18PubMed

Titel: The investigation of possible roles of central 5-HT7 receptors in antipyretic effect mechanism of paracetamol in LPS-induced hyperthermia model of mice
verfasst von: Duygu Kose
Elif Cadirci
Zekai Halici
Busra Sirin
Busra Dincer
Publikationsdatum: 15.07.2019
Verlag: Springer International Publishing
Erschienen in: Inflammopharmacology / Ausgabe 6/2019
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-019-00617-1

Springer Medizin

Abstract

Aim

Materials and methods

Results

Conclusion

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