Genetic deletion of somatostatin receptor 1 alters somatostatinergic transmission in the mouse retina

In the mammalian retina, sparse amacrine cells contain somatostatin-14 (SRIF) which acts at multiple levels of neuronal circuitry through distinct SRIF receptors (sst(1-5)). Among them, the sst(1) receptor has been localised to SRIF-containing amacrime cells in the rat and rabbit retina. Little is known about sst(1) receptor localisation and function in the mouse retina. We have addressed this question in the retina of mice with deletion of sst(1) receptors (sst(1) KO mice). In the retina of wild type (WT) mice, sst(1) receptors are localised to SRIF-containing amacrine cells, whereas in the retina of sst(1) KO mice, sst(1) receptors are absent. sst(1) receptor loss causes a significant increase in retinal levels of SRIF, whereas it does not affect SRIF messenger RNA indicating that sst(1) receptors play a role in limiting retinal SRIF at the post-transcriptional level. As another consequence of sst(1) receptor loss, levels of expression of sst(2) receptors are significantly higher than in control retinas. Together, these findings provide the first demonstration of prominent compensatory regulation in the mouse retina as a consequence of a distinct SRIF receptor deletion. The fact that in the absence of the sst(1) receptor, retinal SRIF increases in concomitance with an increase in sst(2) receptors suggests that SRIF may regulate sst(2) receptor expression and that this regulatory process is controlled upstream by the sst(1) receptor. This finding can be important in the design of drugs affecting SRIF function, not only in the retina, but also elsewhere in the brain. (C) 2003 Elsevier Ltd. All rights reserved.