Somatostatin receptors in wildtype and somatostatin deficient mice and their involvement in nitric oxide physiology in the retina

The present study investigated the localization and density of somatostatin (SRIF) receptor subtypes (sst1-5) and SRIF–nitric oxide (NO) interactions in the retina of wildtype [WT, (+/+)] and somatostatin deficient mice [SRIF (−/−)]. Immunohistochemistry and radioligand binding studies with subsequent autoradiography were performed. Monoclonal antibodies [SRIF, protein kinase C (rod bipolar cells marker), microtubule associated protein 1A (ganglion cell marker)] and polyclonal antibodies (anti-sst1, sst2A, sst4 receptor) were applied to 10–14 μm sections of retinas fixed in paraformaldehyde. NADPH-diaphorase reactivity was assessed histochemically. [125I]LTT SRIF-28 alone or in the presence of MK678 (sst2 agonist) and [125I]Tyr3-octreotide were employed to quantify sst1-5, sst1/4and sst2/5 receptor densities, respectively. sst1, sst2A, and sst4 receptor immunoreactivities were observed in processes of the inner plexiform layer (IPL), rod bipolar, and in ganglion cells and processes, respectively, in WT and SRIF (−/−) mice. Specific [125I]LTT SRIF-28 and [125I]Tyr3-octreotide binding was increased significantly in SRIF (−/−) mice. NADPH-diaphorase staining was localized in photoreceptors and amacrine cells, but not rod bipolar and ganglion cells. Also, NADPH-diaphorase staining was not colocalized with sst1, sst2A or sst4 receptor immunoreactivity. These results demonstrate an upregulation of SRIF receptors in mice lacking SRIF, but no evident SRIF–NO interaction was observed in the mouse retina.