期刊
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
卷 370, 期 2, 页码 91-98出版社
SPRINGER
DOI: 10.1007/s00210-004-0950-5
关键词
somatostatin; receptor agonists and antagonists; transduction pathways; G proteins; knock-out retina
The peptide somatostatin-14 (SRIF) acts in the mammalian retina through its distinct receptors (sst(1-5)). Scarce information is available on SRIF function in the retina, including the elucidation of transduction pathways mediating SRIF action. We have investigated SRIF and SRIF receptor modulation of adenylyl cyclase (AC) activity in both wild-type (WT) retinas and sst(1) or sst(2) knock-out (KO) retinas, which are known to over-express sst(2) or sst(1) receptors respectively. In WT retinas, application of SRIF compounds does not affect forskolin-stimulated AC activity. In contrast, activation of sst(1) or sst(2) receptors inhibits AC in the presence of sst(2) or sst(1) receptor antagonists respectively. Results from sst(1) KO retinas demonstrate that either SRIF or the sst(2) receptor preferring agonist octreotide, pertussis toxin-dependently inhibit AC activity. In contrast, in sst(2) KO retinas, neither SRIF nor CH-275, an sst(1) receptor agonist, are found to influence AC activity. As revealed by immunoblotting experiments, in sst(1) KO retinas, levels of G(o)alpha proteins are 60% higher than in WT retinas and this increase in G(o)alpha protein levels is concomitant with an increase in sst(2A) receptor expression. We conclude that interactions between sst(1) and sst(2) receptors may prevent SRIF effects on AC activity. In addition, we suggest that the density of sst(2) receptors and/or G(o)alpha proteins may represent the rate-limiting factor for the sst(2) receptor-mediated inhibition of AC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据