Ricci Alberto, Sabbatini Maurizio, Tomassoni Daniele, Mignini Fiorenzo, Petrelli Cristina, Amenta Francesco
Dipartimento di Scienze Cardiovascolari e Respiratorie, Università La Sapienza, 00160 Roma, Italy.
Clin Exp Hypertens. 2002 Oct-Nov;24(7-8):715-26. doi: 10.1081/ceh-120015347.
Dihydropyridine (DHP)-type Ca2+ antagonists block primarily L-type Ca2+ channels and are used in the therapy of hypertension. They were also proposed for the treatment of several central nervous system disorders. In brain, these compounds bind both neuronal and vascular Ca2+ channels, but no studies have evaluated comparatively their density at neuronal and vascular level. This study has analyzed the pharmacological profile and the anatomical localization of L-type Ca2+ channels in rat frontal cortex, hippocampus and in forebrain pial and intracerebral arteries by radioligand binding assay and high resolution light microscope autoradiography. The DHP derivative [3H]nicardipine was used as a radioligand. Binding of [3H]nicardipine was consistent with the labeling of L-type Ca2+ channels. In frontal cortex, the highest density of binding sites was found in nerve cell body region, followed by the neuropil and the wall of intracerebral arteries. In hippocampus, the density of binding sites was higher in the nerve cell body region than in the neuropil of CA1, CA3, and CA4 subfields. In the dentate gyrus, a higher density of silver grains was developed in neuropil than in nerve cell body of granule neurons. With the exception of dentate gyrus, neuronal binding sites were more expressed than vascular binding sites in the hippocampus. In pial arteries [3H]nicardipine binding density decreased concomitant with the reduction of vessel diameter, whereas in intracerebral arteries [3H]nicardipine binding density displayed an opposite pattern. The above findings indicate that in brain the density of neuronal L-type Ca2+ channels was significantly higher than that of vascular ones. This may account for more pronounced neuronal than vascular effects after pharmacological manipulation of cerebral Ca2+ channels.
二氢吡啶（DHP）类钙拮抗剂主要阻断L型钙通道，用于治疗高血压。它们也被提议用于治疗几种中枢神经系统疾病。在大脑中，这些化合物与神经元和血管的钙通道都有结合，但尚无研究比较它们在神经元和血管水平的密度。本研究通过放射性配体结合测定和高分辨率光学显微镜放射自显影分析了大鼠额叶皮质、海马以及前脑软脑膜和脑内动脉中L型钙通道的药理学特征和解剖定位。DHP衍生物[3H]尼卡地平用作放射性配体。[3H]尼卡地平的结合与L型钙通道的标记一致。在额叶皮质中，结合位点密度最高的区域是神经细胞体区域，其次是神经纤维网和脑内动脉壁。在海马中，神经细胞体区域的结合位点密度高于CA1、CA3和CA4亚区的神经纤维网。在齿状回中，颗粒神经元神经纤维网中的银粒密度高于神经细胞体。除齿状回外，海马中神经元结合位点的表达高于血管结合位点。在软脑膜动脉中，[3H]尼卡地平结合密度随血管直径的减小而降低，而在脑内动脉中，[3H]尼卡地平结合密度呈现相反的模式。上述发现表明，在大脑中，神经元L型钙通道的密度显著高于血管L型钙通道。这可能解释了在对脑钙通道进行药理学操作后，神经元效应比血管效应更明显的原因。
