Somatostatin receptor activation (sst(1) -sst(5) ) differentially influences human retinal pigment epithelium cell viability.
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.
Papadaki
Thekla
T
Department of Pharmacology, Faculty of Medicine, University of Crete, Crete, Greece.
Tsilimbaris
Miltiadis
M
Pallikaris
Ioannis
I
Thermos
Kyriaki
K
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
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