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Yoshiaki Tagawa, Kousuke Noda, Ryo Miyamoto, Ken-ichi Otsuguro, Erdal Tan Ishizuka, Saori Inafuku, Takeshi Ohguchi, Atsuhiro Kanda, Susumu Ishida, Corneal Cell Biology; Rebamipide Reduces the Response to Capsaicin in Sensory Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):309.
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© ARVO (1962-2015); The Authors (2016-present)
Rebamipide, an amino acid derivative of 2-(1H)-quinolinone, is known to increase mucin production, which reportedly contribute to alleviation of symptoms in patients with dry eye, in conjunctival goblet cells and corneal epithelial cells. However, the mechanism underlying the pharmacological effect of rebamipide in dry eye remains obscure. We previously reported that topical administration of rebamipide ameliorates hyperalgesia in patients with dry eye, indicating that rebamipide might regulate the response of corneal sensory nerve. In this study, we examined the effect of rebamipide on sensory nerve using rattus sensory dorsal root ganglion (DRG) cells.
After euthanasia, DRG cells were collected from the dorsal spinal nerve root of rattus and cultured with Dulbecco's modified eagle medium. After 24 hours of incubation, the cells were transferred to imaging chamber and stimulated with capsaicin perfusion (10-7 mol/l), agonist of transient receptor potential V1 (TRPV1), for 4 times during experiments. After the first capsaicin stimulation, rebamipide solution (10-4 mol/l, rebamipide group) or vehicle solution (0.1% DMSO, control group) was continuously perfused in the chamber until the end of experiment. Activation of TRPV1, receptor for pain sensation, was evaluated by measurement of intracellular calcium concentration with fura-2 imaging system after capsaicin stimulation. The value of calcium concentration was normalized by the peak concentration of the first administration of capsaicin.
In control group, intracellular calcium concentration originated from the response to capsaicin via TRPV1 in DRG cells, was maintained from the second to the fourth stimulation of capsaicin (0.95 ± 0.07, 1.04 ± 0.08 and 1.05 ± 0.09, arbitrary unit, n = 67). By contrast, in rebamipide group, the concentrations of intracellular calcium were gradually reduced and showed significant decrease at the third and forth stimulation of capsaicin compared with those at the first stimulation of capsaicin alone (0.78 ± 0.12, 0.69 ± 0.06* and 0.55 ± 0.08*, arbitrary unit, *P < 0.05, n = 49).
The current data demonstrated that rebamipide suppressed the response of TRPV1 stimulated with capsaicin in DRG cells. This indicates that rebamipide reduces pain sensation in sensory ganglion cells, which may relate to hyperalgesia and subjective symptoms in patients with dry eye.
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