Bigiani Albertino, Petrucci Cristina, Ghiaroni Valeria, Dal Monte Massimo, Cozzi Andrea, Kreienkamp Hans-Jurgen, Richter Dietmar, Bagnoli Paola
Dipartimento di Scienze Biomediche, Sezione di Fisiologia, Università di Modena e Reggio Emilia via Campi 287, 41100 Modena, Italy.
Brain Res. 2004 Oct 29;1025(1-2):177-85. doi: 10.1016/j.brainres.2004.07.083.
Somatostatin-14 (SRIF) and its receptors (sst(1-5)) are found in the mammalian retina. However, scarce information is available on the role of the somatostatinergic system in retinal physiology. We have recently used gene-knockout technology to gain insights into the function of sst(1) and sst(2) receptors in the mouse retina. The sst(1) receptor localizes to SRIF-containing amacrine cells, whereas the sst(2) receptor localizes to several retinal cell populations including rod bipolar cells (RBCs). Molecular data indicate that, in retinas with deletion of the sst(1) receptor (sst(1) KO), sst(2) receptors become overexpressed in concomitance with an increased level of retinal SRIF. To test whether this up-regulation of sst(2) receptors correlates with altered sst(2) receptor physiology, we studied the effect of sst(2) receptor activation on potassium current (I(K)) in isolated RBCs and glutamate release in retina explants. Both I(K) and glutamate release are known to be negatively modulated by sst(2) receptors in the mammalian retina. We used octreotide, a SRIF analogue, to activate selectively sst(2) receptors. Patch-clamp recordings from isolated RBCs indicated that the sst(2) receptor-mediated inhibition of I(K) was significantly larger in sst(1) KO than in control retinas. In addition, HPLC measurements of glutamate release in sst(1) KO retinal explants demonstrated that the sst(2) receptor-mediated inhibition of K(+)-evoked glutamate release was also significantly larger than in control retinas. As a whole, these findings indicate that the overexpression of sst(2) receptors in sst(1) KO retinas can be correlated to an enhanced function of sst(2) receptors. The level of expression of sst(2) receptors may therefore represent a key step in the regulation of sst(2) receptor-mediated responses, at least in the retina.
生长抑素 - 14（SRIF）及其受体（sst(1 - 5)）存在于哺乳动物视网膜中。然而，关于生长抑素能系统在视网膜生理学中的作用，目前可用信息稀少。我们最近利用基因敲除技术来深入了解sst(1)和sst(2)受体在小鼠视网膜中的功能。sst(1)受体定位于含SRIF的无长突细胞，而sst(2)受体定位于包括视杆双极细胞（RBCs）在内的多个视网膜细胞群体。分子数据表明，在sst(1)受体缺失的视网膜（sst(1) KO）中，sst(2)受体伴随视网膜SRIF水平升高而过度表达。为了测试sst(2)受体的这种上调是否与sst(2)受体生理学改变相关，我们研究了sst(2)受体激活对分离的RBCs中钾电流（I(K)）以及视网膜外植体中谷氨酸释放的影响。已知在哺乳动物视网膜中，I(K)和谷氨酸释放均受到sst(2)受体的负调节。我们使用生长抑素类似物奥曲肽来选择性激活sst(2)受体。从分离的RBCs进行的膜片钳记录表明，sst(2)受体介导的对I(K)的抑制在sst(1) KO中比在对照视网膜中显著更大。此外，对sst(1) KO视网膜外植体中谷氨酸释放的高效液相色谱测量表明，sst(2)受体介导的对K⁺诱发的谷氨酸释放的抑制也比对照视网膜中显著更大。总体而言，这些发现表明sst(1) KO视网膜中sst(2)受体的过度表达可能与sst(2)受体功能增强相关。因此，sst(2)受体的表达水平可能代表了sst(2)受体介导反应调节中的关键步骤，至少在视网膜中是这样。
