Park J, Chiba T, Yokotani K, DelValle J, Yamada T
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0362.
Am J Physiol. 1989 Aug;257(2 Pt 1):G235-41. doi: 10.1152/ajpgi.1989.257.2.G235.
Somatostatin is known to have inhibitory effects on the release and action of a wide variety of gut peptides. Previous studies in vivo have suggested a potential inhibitory role for somatostatin even on its own secretion. To determine whether this autoregulatory effect is the result of a direct action of the peptide on the cell that is responsible for its secretion, we examined the effect of a non-immunoreactive but biologically active analogue of somatostatin ([Leu8-D-Trp22-Tyr25]S28) on release of somatostatin-like immunoreactivity (SLI) from isolated canine fundic D-cells. We identified somatostatin binding sites with dissociation constants of 1.2 X 10(-9) and 3.8 X 10(-8) M that coenriched with D-cells. Somatostatin 14, somatostatin 28, and [Leu8-D-Trp22-Tyr25]S28 were equivalent in displacing 125I-[Leu8-D-Trp22-Tyr25]S28 from the binding sites. [Leu8-D-Trp22-Tyr25]S28 inhibited SLI release from D-cells stimulated with (DBcAMP), and pentagastrin. Pertussis toxin pretreatment prevented the inhibitory effects of [Leu8-D-Trp22-Tyr25]S28 on both SLI secretion and cAMP accumulation by on both SLI secretion and cAMP accumulation by D-cells stimulated with epinephrine and forskolin. In contrast, [Leu8-D-Trp22-Tyr25]S28 inhibition of SLI release induced by DBcAMP and pentagastrin was not altered by pertussis toxin. Our data suggest that somatostatin autoregulates its own secretion via specific receptors on D-cells. This inhibitory effect is mediated by mechanisms that are both dependent on and independent of pertussis toxin-sensitive inhibitory guanine nucleotide binding proteins.
已知生长抑素对多种胃肠肽的释放和作用具有抑制作用。先前的体内研究表明，生长抑素甚至对其自身分泌也可能具有潜在的抑制作用。为了确定这种自身调节作用是否是该肽对负责其分泌的细胞直接作用的结果，我们研究了一种非免疫反应性但具有生物活性的生长抑素类似物（[亮氨酸8 - D - 色氨酸22 - 酪氨酸25]S28）对分离的犬胃底D细胞释放生长抑素样免疫反应性物质（SLI）的影响。我们鉴定出解离常数为1.2×10^(-9)和3.8×10^(-8) M且与D细胞共同富集的生长抑素结合位点。生长抑素14、生长抑素28和[亮氨酸8 - D - 色氨酸22 - 酪氨酸25]S28在从结合位点置换125I - [亮氨酸8 - D - 色氨酸22 - 酪氨酸25]S28方面效果相当。[亮氨酸8 - D - 色氨酸22 - 酪氨酸25]S28抑制由二丁酰环磷腺苷（DBcAMP）和五肽胃泌素刺激的D细胞释放SLI。百日咳毒素预处理可防止[亮氨酸8 - D - 色氨酸22 - 酪氨酸25]S28对肾上腺素和福斯高林刺激的D细胞的SLI分泌和环磷腺苷（cAMP）积累的抑制作用。相比之下，[亮氨酸8 - D - 色氨酸22 - 酪氨酸25]S28对DBcAMP和五肽胃泌素诱导的SLI释放的抑制作用不受百日咳毒素影响。我们的数据表明，生长抑素通过D细胞上的特异性受体对其自身分泌进行自身调节。这种抑制作用是由既依赖又不依赖百日咳毒素敏感的抑制性鸟嘌呤核苷酸结合蛋白的机制介导的。
