Somatostatin receptor activation (sst(1) -sst(5) ) differentially influences human retinal pigment epithelium cell viability.

Purpose: 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.