The aim of this study was to examine the ability of somatostatin receptor (sst(1)) to regulate the release of somatostatin in rat retina. Immunohistochemistry studies were performed to locate the somatostatin neurons, and radioligand binding to ascertain the presence of sst(1). The neuronal release of somatostatin was examined ex vivo in rat retinal explants in the presence of KCl (50 and 100 mM), and absence of Ca(++) (EGTA; 10 mM). Somatostatin levels, quantified by radioimmunoassay, were increased in the presence of KCl (100 mM, 151%) and attenuated in the absence of Ca(++) (31%). CH275 (sst(1) agonist) reduced the somatostatin levels in a concentration-dependent manner (10(-5)-10(-7) M), and this effect was reversed by NVP-SRA 880 (sst(1) antagonist;10(-5) M). MK678 (sst(2) agonist; 10(-5) M) had no effect. These data suggest an autoreceptor role for sst(1) in retina.