title: Bimatoprost Increases Mechanosensitivity of Trigeminal Ganglion Neurons Innervating the Inner Walls of Rat Anterior Chambers via Activation of TRPA1.
abstract: OBJECTIVE
  Our previous study found that some trigeminal ganglion (TG) nerve endings in the inner walls of rat anterior chambers were mechanosensitive, and transient receptor potential ankyrin 1 (TRPA1) was an essential mechanosensitive channel in the membrane. To address the effect of bimatoprost on the mechanosensitive TG nerve endings in the inner walls of rat anterior chambers, we investigated its effect on their cell bodies in vitro.
  
  
  METHODS
  Rat TG neurons innervating the inner walls of the anterior chambers were labeled by anterior chamber injection of 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine, 4-chlorobenzenesulfonate (FAST DiI). Calcium imaging and whole cell patch clamp were used on neuronal cell bodies to detect the activation effect of TRPA1 channels. Whole cell patch clamp was performed to record the currents induced by drugs and mechanical stimulation. Mechanical stimulation was applied to the neurons by buffer ejection.
  
  
  RESULTS
  Bimatoprost mimicked the effect of TRPA1 agonists, allyl isothiocyanate (AITC), and (R)-(+)-WIN55, 212-2 mesylate salt (WIN) in the TG neurons. Bimatoprost induced Ca(2+) influx in HEK293 cells stably transfected with human TRPA1, but not in untransfected cells as AITC and WIN. Moreover, bimatoprost evoked inward currents via TRPA1 activation in FAST DiI-labeled TG neurons as WIN. Bimatoprost also enhanced mechanosensitivity of FAST DiI-labeled TG neurons via TRPA1 activation.
  
  
  CONCLUSIONS
  Our results indicate that bimatoprost is a novel agonist of TRPA1, and it can enhance mechanosensitivity of TG nerve endings in the inner walls of anterior eye chambers via TRPA1 activation in rats.
authors.affiliation: Department of Ophthalmology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhuangli
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Ophthalmology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qingli
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Fang
authors.affiliation: Department of Ophthalmology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Liu
mesh_terms: D000200:Action Potentials; D000818:Animals; D000867:Anterior Chamber / Q000294:innervation*; D000959:Antihypertensive Agents / Q000494:pharmacology; D000069580:Bimatoprost / Q000494:pharmacology*; D057809:HEK293 Cells; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008465:Mechanoreceptors / Q000187:drug effects / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D018841:HSP90 Heat-Shock Proteins; C549284:TRAP1 protein, rat; D000069580:Bimatoprost