title: Kappa opioid receptor localization and coupling to nitric oxide production in cells of the anterior chamber.
abstract: OBJECTIVE
  The present study was designed to determine whether kappa opioid receptors (KORs) are localized to cells of the inflow and outflow pathways of the eye and if activation of these receptors has an effect on nitric oxide (NO) production, because these effects could play a role in KOR agonist-mediated reduction of IOP.
  
  
  METHODS
  Human nonpigmented ciliary epithelial (NPCE) and trabecular meshwork (HTM-3) cells were treated with spiradoline (SPR), a selective KOR agonist, or estradiol, for 24 hours. Some cells were pretreated with the selective KOR antagonist norbinaltorphimine (norBNI) or the nonselective NO synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) for 30 minutes, followed by the addition of SPR. Immunofluorescent localization of KORs was determined in isolated rabbit iris-ciliary bodies (ICBs) and NPCE and HTM-3 cells.
  
  
  RESULTS
  Immunohistochemical data show the localization of KORs to the rabbit ICB and more specifically to the ciliary epithelial layer. KORs were also found on cell membranes of NPCE and HTM-3 cells. Treatment of both these cell types with spiradoline caused concentration-dependent increases in the release of NO. Spiradoline-induced release of NO from both cell types was inhibited by pretreatment with norBNI and L-NAME.
  
  
  CONCLUSIONS
  Results from this study show the presence of KORs on rabbit ICBs and also on NPCE and HTM cells. Activation of these KORs on both cell types resulted in KOR-mediated increases in NO production. These findings provide evidence that previously demonstrated KOR-mediated reduction in IOP could be caused, in part, by NO production in both the ciliary body and the trabecular meshwork.
authors.affiliation: Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia 30310-1495, USA. krandall@msm.edu
authors.forename: Karen R
authors.initials: KR
authors.lastname: Russell-Randall
authors.forename: Juanita
authors.initials: J
authors.lastname: Dortch-Carnes
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002924:Ciliary Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004728:Endothelium, Corneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D011817:Rabbits; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism*; D014129:Trabecular Meshwork / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000700:Analgesics; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D009569:Nitric Oxide; C051844:norbinaltorphimine; D004958:Estradiol; D009271:Naltrexone; C051272:spiradoline; D019331:NG-Nitroarginine Methyl Ester