title: Somatostatin receptor activation (sst(1) -sst(5) ) differentially influences human retinal pigment epithelium cell viability.
abstract: OBJECTIVE
  To investigate the differential effects of somatostatin and its receptors (sst(1-5) ) on the viability of cultured human retinal pigment epithelium (hRPE) cells.
  
  
  METHODS
  MTT [3 (4, 5-dimethylthiazol-2yl)-2, 5 diphenyltetrazolium bromide], APO Percentage(TM) and trypan blue assays were performed to assess the mechanisms via which somatostatin (10(-10) -10(-4) m) and selective receptor (sst(1-5) ) ligands (10(-12) -10(-4) m) affect cell viability. The effect of orthovanadate (phosphatase inhibitor, 10(-7) -10(-5) m) on somatostatin's (10(-5) m) actions was examined, and western blot analysis was employed to determine the presence of ssts and phosphotyrosine phosphatase SHP-1 in human RPE cells.
  
  
  RESULTS
  Somatostatin and selective ligands for the five somatostatin receptor subtypes (sst(1-5) ) decreased cell viability in a concentration-dependent manner. The observed decrease in cell number was partly because of apoptosis via the activation of sst(1) and sst(5) receptors. Activation of sst(2) , sst(3) and sst(4) receptors led to inhibition of cell growth that did not involve apoptosis, but rather antiproliferative actions. SHP-1 was found in the human RPE cells and sodium orthovanadate reversed somatostatin's actions.
  
  
  CONCLUSIONS
  This study provides new information regarding the involvement of ssts in human RPE cell viability and suggests that a pathway involving the phosphotyrosine phosphatase may mediate somatostatin's actions.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Crete, Crete, Greece.
authors.forename: Thekla
authors.initials: T
authors.lastname: Papadaki
authors.forename: Miltiadis
authors.initials: M
authors.lastname: Tsilimbaris
authors.forename: Ioannis
authors.initials: I
authors.lastname: Pallikaris
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Thermos
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D009336:Necrosis; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014343:Trypan Blue / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
chemical_list: D008024:Ligands; D017481:Receptors, Somatostatin; D013778:Tetrazolium Salts; D013844:Thiazoles; C101130:somatostatin receptor type 1; D014638:Vanadates; C094573:somatostatin receptor 5; D013006:Growth Hormone; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C022616:thiazolyl blue; D014343:Trypan Blue