Vasilaki Anna, Papasava Despina, Hoyer Daniel, Thermos Kyriaki
Laboratory of Pharmacology, Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion, 71110 Crete, Greece.
Neuropharmacology. 2004 Sep;47(4):612-8. doi: 10.1016/j.neuropharm.2004.06.008.
The aim of the present study was to examine the function of the somatostatin receptor (sst(1)) in the nucleus accumbens (NAc) of the basal ganglia. Radioligand binding studies were performed in rats to assess the presence of the receptor, while in vivo microdialysis studies were performed to examine its role in somatostatin release. CH-275, which is selective for sst(1), MK-678, selective for sst(2) and L-803,087, selective for sst(4) receptors displaced [(125)I]-Tyr(11)-somatostatin specific binding in a concentration-dependent manner with IC(50) values of 75, 0.21 and 11 nM, respectively. Infusion of CH-275 (10(-5), 10(-6) or 10(-7) M) in the NAc of freely moving rats resulted in a decrease in somatostatin levels only at the concentration of 10(-5) M. This effect was reversed by 10(-5) M of the selective sst(1) antagonist SRA-880. The sst(1) agonist L-797,591 (10(-5) M) mimicked the effect of CH-275, while MK-678 and L-803,087 at the same concentration were unable to influence somatostatin levels. These results provide functional evidence to demonstrate that the sst(1) receptor modulates somatostatin release in the basal ganglia.
本研究的目的是检测基底神经节伏隔核(NAc)中生长抑素受体(sst(1))的功能。在大鼠中进行放射性配体结合研究以评估该受体的存在,同时进行体内微透析研究以检测其在生长抑素释放中的作用。对sst(1)具有选择性的CH - 275、对sst(2)具有选择性的MK - 678以及对sst(4)受体具有选择性的L - 803,087,均以浓度依赖性方式取代[(125)I]-Tyr(11)-生长抑素的特异性结合,其IC(50)值分别为75、0.21和11 nM。在自由活动大鼠的NAc中注入CH - 275(10(-5)、10(-6)或10(-7) M),仅在浓度为10(-5) M时导致生长抑素水平降低。这种效应被10(-5) M的选择性sst(1)拮抗剂SRA - 880逆转。sst(1)激动剂L - 797,591(10(-5) M)模拟了CH - 275的作用,而相同浓度的MK - 678和L - 803,087无法影响生长抑素水平。这些结果提供了功能证据,证明sst(1)受体调节基底神经节中生长抑素的释放。