Sexton P M, McKenzie J S, Mendelsohn F A
University Department of Medicine, Austin and Repatriation General Hospitals, Heidelberg, Victoria, Australia.
Neurochem Int. 1988;12(3):323-35. doi: 10.1016/0197-0186(88)90171-4.
Binding sites for calcitonin and calcitonin gene-related peptide are widely distributed in the central nervous system. In this study, binding of [(125)I]-alpha-rat calcitonin gene-related peptide and [(125)I]-salmon calcitonin in adjacent sections of rat brain revealed clearly distinct patterns of binding in most regions although in some restricted areas such as parts of the ventral striatum, including the nucleus accumbens, there was some overlap in the patterns of binding. In the primary olfactory cortex, which bound only calcitonin gene-related peptide, salmon calcitonin was very weak in inhibiting the binding of calcitonin gene-related peptide. In the nucleus accumbens, high affinity binding of calcitonin and calcitonin gene-related peptide at their homologous receptors was observed, with affinity constants for calcitonin and calcitonin gene-related peptide of 1.4 x 10(9) M(?1) and 1.2 x 10(9) M(?1) respectively. Cross competition studies in this nucleus demonstrated that salmon calcitonin was able to compete for [(125)I]-rat calcitonin gene-related peptide labelled sites with high affinity, with an affinity constant of 0.8 x 10(9) M(?1). However, rat calcitonin gene-related peptide was less potent in inhibiting the binding of [(125)I]-salmon calcitonin labelled sites with only 28% inhibition at 10(?6)M. Further characterization of the calcitonin sensitive calcitonin gene-related peptide labelled sites demonstrated that a range of calcitonin analogs inhibited the binding of [(125)I]-rat calcitonin gene-related peptide with the same order of potency as the analogs competed for [(125)I]-salmon calcitonin labelled sites. Digital substraction mapping revealed calcitonin-sensitive calcitonin gene-related peptide binding sites over parts of the ventral striatum, including mid-caudal nucleus accumbens and fundus striati; over the lateral border of the lateral bed nucleus of the stria terminalis; part of the central amygdaloid nucleus; the organum vasculosum of the lamina terminalis and area postrema and over the wings of the dorsal raphe. These results demonstrate the existence of a new subtype of calcitonin/calcitonin gene-related peptide binding site, which has high affinity for the two otherwise biochemically distinct peptides.
降钙素及降钙素基因相关肽的结合位点广泛分布于中枢神经系统。在本研究中，[(125)I] - α - 大鼠降钙素基因相关肽和[(125)I] - 鲑鱼降钙素在大鼠脑相邻切片中的结合显示，尽管在某些局限区域，如腹侧纹状体的部分区域（包括伏隔核），结合模式存在一些重叠，但在大多数区域，其结合模式明显不同。在仅结合降钙素基因相关肽的初级嗅觉皮层中，鲑鱼降钙素对降钙素基因相关肽结合的抑制作用非常微弱。在伏隔核中，观察到降钙素及降钙素基因相关肽在其同源受体上的高亲和力结合，降钙素和降钙素基因相关肽的亲和常数分别为1.4×10(9) M(?1)和1.2×10(9) M(?1)。在该核中的交叉竞争研究表明，鲑鱼降钙素能够以高亲和力竞争[(125)I] - 大鼠降钙素基因相关肽标记的位点，亲和常数为0.8×10(9) M(?1)。然而，大鼠降钙素基因相关肽在抑制[(125)I] - 鲑鱼降钙素标记位点的结合方面效力较低，在10(?6)M时仅有28%的抑制率。对降钙素敏感的降钙素基因相关肽标记位点的进一步表征表明，一系列降钙素类似物抑制[(125)I] - 大鼠降钙素基因相关肽结合的效力顺序，与这些类似物竞争[(125)I] - 鲑鱼降钙素标记位点的效力顺序相同。数字减法映射显示，降钙素敏感的降钙素基因相关肽结合位点分布于腹侧纹状体的部分区域，包括中尾段伏隔核和纹状体底；终纹床核外侧边界；中央杏仁核的一部分；终板血管器和最后区以及背侧中缝核的侧翼。这些结果表明存在一种新的降钙素/降钙素基因相关肽结合位点亚型，其对这两种在生化性质上原本不同的肽具有高亲和力。
