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

Abstract

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.

Prostaglandin D2 effects and DP1/DP2 receptor distribution in guinea pig urinary bladder out‐flow region

“…who showed that DP 1 and DP 2 receptors are present in guinea pig oesophageal nodose ganglia by immunostaining and Western blot with similar antibody, and by RT‐PCR 29. Presently, in male guinea pig trigone and proximal urethra, we found both DP 1 and DP 2 receptors located in the urothelium and smooth muscle and that DP 1 receptors were prominent on the membranes of smooth muscle cells, in agreement with our previous study on bladder detrusor 18.…”

Protective Role of the Hepatic Vagus Nerve against Liver Metastasis in Mice

“…For example, cholecystokinin and serotonin act via vagal afferent fibers to transmit gastrointestinal information to the brain [23]. Vagus afferent nerves are also known to be activated in response to various substances, such as interleukin 1β [24], prostaglandin D 2 , and reactive oxygen species [25, 26]. Interestingly, Gidron et al [27] suggested that the vagus nerve can transmit information about cancer progression to the brain through peripheral proinflammatory cytokines.…”

A perspective on stem cell modeling of amyotrophic lateral sclerosis

“…Agonizing DP1 in mast cells using BW 245C caused these immune cells to induce an increase in neuronal excitability. 77,78 This observation is of particular interest given that it has recently been shown that conditioned media from SOD1G93A glia can induce motor neuron hyperexcitability in rat spinal cord slices. 27 Further studies of whether activated microglia share some properties with mast cells may be warranted.…”

“…76 Additional experiments have also implicated DP1 in mast cell induced neuronal hyperexcitability. 77,78 In these studies DP1 inhibition by BW A868C reduced the levels of extraneous firing when mast cells were co-cultured with primary neurons. Agonizing DP1 in mast cells using BW 245C caused these immune cells to induce an increase in neuronal excitability.…”