title: The antinociception of oxytocin on colonic hypersensitivity in rats was mediated by inhibition of mast cell degranulation via Ca(2+)-NOS pathway.
abstract: This study was conducted to investigate the effects of oxytocin (OT) on visceral hypersensitivity/pain and mast cell degranulation and the underlying mechanisms. We found that oxytocin receptor (OTR) was expressed in colonic mast cells in humans and rats, as well as in human mast cell line-1 (HMC-1), rat basophilic leukemia cell line (RBL-2H3) and mouse mastocytoma cell line (P815). OT decreased 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity, colonic mast cell degranulation and histamine release after mast cell degranulation in rats. Also, OT attenuated the compound 48/80 (C48/80)-evoked histamine release in P815 cells and inward currents, responsible for the mast cell degranulation, in HMC-1, RBL-2H3 and P815 cells. Moreover, these protective effects of OT against visceral hypersensitivity and mast cell degranulation were eliminated by coadministration of OTR antagonist atosiban or a nonselective inhibitor of nitric oxide synthase (NOS), NG-Methyl-L-arginine acetate salt (L-NMMA). Notably, OT evoked a concentration-dependent increase of intracellular Ca(2+) in HMC-1, RBL-2H3 and P815 cells, which was responsible for the activation of neuronal NOS (NOS1) and endothelial NOS (NOS3). Our findings strongly suggest that OT might exert the antinociception on colonic hypersensitivity through inhibition of mast cell degranulation via Ca(2+)-NOS pathway.
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Gong
authors.affiliation: Central Hospital of Zibo, Zibo, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Han
authors.affiliation: Liaocheng People's Hospital, Liaocheng, China.
authors.forename: Chuanfei
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, China.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, China.
authors.forename: Kejing
authors.initials: K
authors.lastname: Liu
authors.affiliation: Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Geng
authors.affiliation: Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Shaozhuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, China.|Provincial Key Lab of Mental Disorder, School of Medicine, Shandong University, China.
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Liu
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015550:Cell Degranulation / Q000187:drug effects*; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control; D003106:Colon / Q000166:cytology / Q000473:pathology; D005071:Evoked Potentials / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018613:Microscopy, Confocal; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology* / Q000627:therapeutic use; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000700:Analgesics; D018045:Receptors, Oxytocin; C047046:atosiban; D019323:omega-N-Methylarginine; D010121:Oxytocin; D014302:Trinitrobenzenesulfonic Acid; D019001:Nitric Oxide Synthase; D002118:Calcium; D014668:Vasotocin