Niehoff D L, Mudge A W
EMBO J. 1985 Feb;4(2):317-21. doi: 10.1002/j.1460-2075.1985.tb03631.x.
The neuropeptide somatostatin potentiates beta-adrenergic receptor-mediated cAMP formation in astrocytes derived from neonatal rat cortex but does not affect cAMP levels by itself. beta-Adrenergic receptors in these cells can be specifically labeled with the high affinity antagonist [125I] cyanopindolol ([125I]CYP). In addition, astrocytes display both high and low affinity binding sites for the agonist isoproterenol, which are thought to represent receptors which are coupled or uncoupled, respectively, to the guanine nucleotide regulatory protein. We find that somatostatin does not modify beta-receptor density, nor receptor affinity for either the antagonist ([125I]CYP) or for the agonist isoproterenol. In the presence of the guanine nucleotide analogue, Gpp(NH)p, only low affinity (uncoupled) displacement of [125I]CYP binding by isoproterenol is observed. However, somatostatin (1 microM), when added to the cells together with Gpp(NH)p, prevents the nucleotide-induced loss of the high affinity (coupled) component of agonist displacement. This result suggests that somatostatin increases noradrenaline-induced cAMP production by enhancing coupling between the beta-receptor and the stimulatory guanine nucleotide regulatory protein.
神经肽生长抑素可增强新生大鼠皮质星形胶质细胞中β-肾上腺素能受体介导的环磷酸腺苷（cAMP）生成，但自身并不影响cAMP水平。这些细胞中的β-肾上腺素能受体可用高亲和力拮抗剂[125I]氰胍心安（[125I]CYP）进行特异性标记。此外，星形胶质细胞对激动剂异丙肾上腺素显示出高亲和力和低亲和力结合位点，据认为分别代表与鸟嘌呤核苷酸调节蛋白偶联或未偶联的受体。我们发现生长抑素不会改变β受体密度，也不会改变受体对拮抗剂（[125I]CYP）或激动剂异丙肾上腺素的亲和力。在存在鸟嘌呤核苷酸类似物Gpp(NH)p的情况下，仅观察到异丙肾上腺素对[125I]CYP结合的低亲和力（未偶联）置换。然而，当生长抑素（1μM）与Gpp(NH)p一起添加到细胞中时，可防止核苷酸诱导的激动剂置换高亲和力（偶联）成分的丧失。这一结果表明，生长抑素通过增强β受体与刺激性鸟嘌呤核苷酸调节蛋白之间的偶联来增加去甲肾上腺素诱导的cAMP生成。
