Autoradiographic visualization of [3H]nitrendipine binding sites in rat brain: localization to synaptic zones.
Autoradiographic visualization of [3H]nitrendipine binding sites in rat brain: localization to synaptic zones.
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大鼠大脑中[3H]尼群地平结合位点的放射自显影可视化：突触区的定位。
DOI：
10.1016/0014-2999(82)90120-0
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发表时间：
1982
影响因子：
5
通讯作者：
Snyder,SH
中科院分区：
文献类型：
--
作者：
Murphy,KM;Gould,RJ;Snyder,SH
有机钙拮抗剂通过血管平滑肌中的电压依赖性钙通道发挥治疗作用。这些药物的几种不同化学类别的药理学特性有所不同。最近，我们（MurPhY 和 Snyder，1982；Gould 等，1982）和其他人（Bolger 等，1982；Ehlert 等，1982）鉴定了 [3H]-尼群地平结合位点，其具有二氢吡啶类钙拮抗剂药理作用受体的特性。由于维拉帕米、D-600 和地尔硫卓与这些位点的相互作用很弱，因此它们可能通过不同的识别位点发挥作用，这些识别位点可能与二氢吡啶受体变构连接（Ehlert 等，1982）。 [3H] 尼群地平在大脑内结合的显着区域差异表明这些位点主要并不在血管上（Gould 等，1982）。在本研究中，我们表明大脑中的[3H]尼群地平受体定位于神经纤维，表明在突触功能中发挥作用。放射自显影图是通过Young和Kuhar (1979)的方法使用8/xm厚的载玻片安装的大鼠脑切片生成的。使用溶于 0.17 M Tris-HCl 缓冲液（pH 7.6）的 0.2 nM [3H] 尼群地平，在不存在或存在 60 nM 硝苯地平的情况下，在 24℃ 下测定 30 分钟，测定特异性和非特异性结合。初步实验表明，该结合是饱和的、可逆的，并且显示出与脑匀浆中测量的位点相似的药理学特征（MurPhy 和
Organic calcium antagonists exert therapeutic actions via voltage dependent calcium channels in vascular smooth muscle. The several different chemical classes of these drugs differ in pharmacologic properties. Recently we (MurPhY and Snyder, 1982; Gould et al., 1982) and others (Bolger et al., 1982; Ehlert et al., 1982) have identified [3H]-nitrendipine binding sites which have properties of receptors for the pharmacologic actions of the dihydropyridine class of calcium antagonists. Since verapamil, D-600 and diltiazem only weakly interact with these sites, they presumably act via distinct recognition sites which may be linked allosterically to the dihydropyridine receptors (Ehlert et al., 1982). The marked regional variations of [3H] nitrendipine binding within the brain suggest that these sites are not primarily on blood vessels (Gould et al., 1982). In the present study we show that [3H] nitrendipine receptors in the brain are localized to neuropil suggesting a role in synaptic function.Autoradiograms were generated by the method of Young and Kuhar (1979) using 8/xm thick slide-mounted rat brain sections. Specific and non-specific binding was determined using 0.2 nM [3H] nitrendipine in 0.17 M Tris-HC1 buffer, pH 7.6, in the absence or presence of 60 nM nifedipine for 30 min at 24 C. Preliminary experiments indicated that the binding was saturable, reversible and showed a pharmacologic profile similar to sites measured in brain homogenates (MurPhy and