描述生长抑素的神经元作用。

A D Blake, A C Badway, M Z Strowski
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引用次数: 23

摘要

生长抑素释放抑制因子;SRIF通过与一系列高度同源的整膜受体(sst(1) -sst(5))相互作用启动其生物活性。SRIF神经元的作用是调节蛋白磷酸化水平,控制第二信使的产生和调节神经元膜电位。最近,我们对SRIF神经生物学的理解是由新的药理学和分子生物学工具驱动的。SRIF受体亚型特异性抗体已经确定了该受体家族的独特但重叠的表达模式,多个亚型在中枢和外周神经系统中共定位。这种复杂的表达谱在一定程度上阻碍了通过受体蛋白的同源和异寡聚化来确定每种受体在神经系统中的作用的努力。然而,最近SRIF受体亚型选择性配体的发现,以及体外和体内灭活SRIF受体基因模型的补充,现在提供了清晰描述每种受体神经元作用的机会。这些药理学,免疫学和分子生物学方法的融合扩展了我们对SRIF神经生物学的理解,同时为SRIF研究提供了新的治疗途径。
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Delineating somatostatin's neuronal actions.

Somatostatin (somatotropin release inhibitory factor; SRIF) initiates its biological activity by interacting with a family of highly homologous integral membrane receptors (sst(1) -sst(5)). SRIF neuronal actions regulate protein phosphorylation levels, control second messenger production and modulate neuronal membrane potential. Recently, our understanding of SRIF neurobiology has been driven by new pharmacological and molecular biological tools. SRIF receptor subtype specific antibodies have identified a distinctive, yet overlapping, expression pattern for this receptor family, with multiple subtypes co-localizing in the central and peripheral nervous system. This complex expression profile has confounded efforts to establish each receptor's role in the nervous system in part by the possible homo- and heteroligomerization of the receptor proteins. However, the recent discovery of SRIF receptor subtype selective ligands, supplemented by in vitro and in vivo models with inactivated SRIF receptor genes, now provides opportunities to clearly delineate each receptor's neuronal role. The convergence of these pharmacologic, immunologic and molecular biologic approaches extend our understanding of SRIF neurobiology while promising new therapeutic avenues for SRIF research.

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