September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Suppression of Cholecystokinin Response by Rebamipide in Trigeminal Ganglion Cells
Author Affiliations & Notes
  • Yoshiaki Tagawa
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Kousuke Noda
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Ryo Miyamoto
    Laboratory of Pharmacology, Hokkaido University Graduate School of Veterinary Medicine, Sapporo, Japan
  • Ken-ichi Otsuguro
    Laboratory of Pharmacology, Hokkaido University Graduate School of Veterinary Medicine, Sapporo, Japan
  • Erdal Tan Ishizuka
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Takeshi Ohguchi
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Atsuhiro Kanda
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Susumu Ishida
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Footnotes
    Commercial Relationships   Yoshiaki Tagawa, None; Kousuke Noda, None; Ryo Miyamoto, None; Ken-ichi Otsuguro, None; Erdal Tan Ishizuka, None; Takeshi Ohguchi, None; Atsuhiro Kanda, None; Susumu Ishida, None
  • Footnotes
    Support  This work was supported by Otsuka pharmaceutical grant PJ42140023.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 414. doi:
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      Yoshiaki Tagawa, Kousuke Noda, Ryo Miyamoto, Ken-ichi Otsuguro, Erdal Tan Ishizuka, Takeshi Ohguchi, Atsuhiro Kanda, Susumu Ishida; Suppression of Cholecystokinin Response by Rebamipide in Trigeminal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):414.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Rebamipide ophthalmic suspension is widely used in the treatment of dry eye syndromes and is known to repair the milieu of keratoconjunctival epithelia and increase mucin production in conjunctival goblet cells. In addition to the restoration of ocular surface, we also found that rebamipide suppressed the activation of transient receptor potential channel subfamily member V1 (TRPV1) with capsaicin in rat sensory dorsal root ganglion (DRG) cells (ARVO2015). Our data indicated that topical administration of rebamipide also ameliorates subjective symptoms, i.e. hyperalgesia, in patients with dry eye through the silencing of sensory nerve cells. In this study, we further explored the pharmacological property of rebamipide to improve the symptoms in patients with dry eye.

Methods : After euthanasia, trigeminal ganglion (TG) cells were collected from wistar rats (0 to 2-week-old) and cultured with Dulbecco's modified eagle medium. After 24-hour culture, the cells were transferred to the imaging chamber and stimulated with 3-time perfusion of cholecystokinin (CCK, 10-7mol/l), one of the neuropeptides that increases the calcium concentration in TG cells, for 20 seconds. Prior to the second stimulation, either vehicle solution (0.1% DMSO, control group) or rebamipide solution (3x10-4mol/l, rebamipide group) was also perfused for 30 seconds. Intracellular calcium concentrations in TG cells were measured by fura-2 dye imaging system.

Results : In the control group, the increase of intracellular calcium concentration did not change through the 3-time stimulations of CCK (7.73±2.95nM, 7.10±2.44nM, 6.59±2.16nM, respectively, n=47). However, in the rebamipide group, the increase of intracellular calcium concentration by CCK significantly decreased at the second stimulation (8.03±3.12nM, 1.61±0.42nM*, 7.76±2.59nM, *P<0.05, n=41), clearly demonstrating that rebamipide suppresses the response against CCK in TG cells.

Conclusions : The blockade of CCK stimulation is known to suppress neuropathic pain. Therefore, the present data demonstrated that rebamipide suppressed the response of CCK in TG cells, suggesting that rebamipide silences the sensory nerve cells of cornea, TG cells, through blockade of CCK-CCK receptors axis.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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