Epelbaum J, Tapia-Arancibia L, Alonso G, Astier H, Kordon C
Neuroendocrinology. 1986;44(2):255-9. doi: 10.1159/000124653.
The site of action of the inhibitory effect of somatostatin (SRIF) on its own release was studied by: (1) measuring SRIF release in vitro from tissue preparations containing either the proximal (periventricular hypothalamus) or the distal (median eminence) portions of the hypothalamic SRIF neurons, and (2) immunocytochemical investigation of the interconnections occurring between SRIF neuronal elements in these hypothalamic regions. In vitro, a biologically active, but noncross-reacting SRIF analog (D-Trp8 SRIF) in the RIA, inhibited 25 mM K+ induced SRIF release from anterior periventricular hypothalamic tissues. The inhibitory effect of D-Trp8 SRIF was dose-dependent, maximal at 10(-7) M, and restricted to this anterior region, since median-eminence SRIF release was not modified by the presence of D-Trp8 SRIF. Additionally, LHRH release from anterior periventricular hypothalamus was unchanged in the presence of D-Trp8 SRIF. In the periventricular nucleus, perikarya and dendrites of labeled SRIF neurons showed frequent apposition of their limiting membranes. Classical synapses were also observed between SRIF-containing axonal processes and labeled perikarya or dendrites. Although membrane appositions between neighboring SRIF axons frequently occurred in the median eminence, no synaptic-like SRIF-SRIF connections could be detected at this level. The data demonstrate a direct inhibitory action of a SRIF agonist on the anterior periventricular hypothalamic release of the peptide. This effect correlates well with the occurrence of SRIF-SRIF synapses in this region; suggesting that SRIF exerts a negative feedback in the control of its own release through autoreceptors located on the perikarya or dendrites of SRIF-containing neurons.
通过以下方法研究了生长抑素(SRIF)对自身释放的抑制作用的作用位点:(1)在体外测量含有下丘脑SRIF神经元近端(室周下丘脑)或远端(正中隆起)部分的组织制剂中SRIF的释放,以及(2)对这些下丘脑区域中SRIF神经元元件之间发生的相互连接进行免疫细胞化学研究。在体外,放射免疫分析中一种具有生物活性但无交叉反应的SRIF类似物(D-Trp8 SRIF)抑制了25 mM K⁺诱导的室周下丘脑前部组织中SRIF的释放。D-Trp8 SRIF的抑制作用呈剂量依赖性,在10⁻⁷ M时最大,且仅限于该前部区域,因为正中隆起处的SRIF释放不受D-Trp8 SRIF存在的影响。此外,在D-Trp8 SRIF存在的情况下,室周下丘脑前部的促黄体生成素释放激素(LHRH)释放没有变化。在室周核中,标记的SRIF神经元的胞体和树突显示其限制膜频繁并列。在含有SRIF的轴突过程与标记的胞体或树突之间也观察到了典型的突触。尽管在正中隆起处相邻的SRIF轴突之间经常发生膜并列,但在该水平未检测到类似突触的SRIF-SRIF连接。数据表明SRIF激动剂对该肽在室周下丘脑前部的释放具有直接抑制作用。这种作用与该区域中SRIF-SRIF突触的出现密切相关;表明SRIF通过位于含SRIF神经元的胞体或树突上的自身受体在其自身释放的控制中发挥负反馈作用。