The antinociception of oxytocin on colonic hypersensitivity in rats was mediated by inhibition of mast cell degranulation via Ca2+-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 Ca2+ 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 Ca2+-NOS pathway.

Peripheral inflammatory pain sensitisation is independent of mast cell activation in male mice

“…It cannot be ruled out that at this high concentration compound 48/80 may even be toxic to neurons, as intracellular Ca ++ accumulation remains constant after several minutes after the application of the drug. Nevertheless, our data clearly demonstrate that DRG neurons are capable of responding to compound 48/80, at a dose known to cause MC degranulation (10μg/ml) [13; 33; 58; 72; 75; 78] and independent of the presence of any other cell type. These findings further demonstrate the unspecificity of compound 48/80 and emphasise the importance of developing new models, such as the Mcpt5-iDTR transgenic model, to study MC in context of pain.…”

Annexin A1 Mimetic Peptide Ac2-26 Modulates the Function of Murine Colonic and Human Mast Cells

“…Many studies have shown the role of MCs in visceral hypersensitivity reaction mechanisms based on in vitro assays using human HMC-1 cell line (52)(53)(54). For that reason, the human HMC-1 cell line is considered a good model to evaluate the role of AnxA1 on cell function.…”

Eucalyptus oil reduces allergic reactions and suppresses mast cell degranulation by downregulating IgE-FcεRI signalling

“…Measurement of intracellular calcium levels. Intracellular calcium levels were measured using a Calcium kit Fluo 4 (Dojindo Laboratories, Kumamoto, Japan) according to the manufacturer's instructions 45,46 . BMMCs were seeded at 4.0 × 10 4 cells/well in a 96-well black culture plate and sensitised with anti-DNP IgE (50 ng/mL) at 37 °C overnight.…”