Knock G A, Wharton J, Gaer J A, Yacoub M H, Taylor K M, Polak J M
Department of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Eur J Pharmacol. 1992 Sep 4;219(3):415-25. doi: 10.1016/0014-2999(92)90483-k.
Quantitative in vitro autoradiographic techniques were used to localize and characterize 125I-labelled human calcitonin gene-related peptide ([125I]hCGRP) binding sites in sections of bovine left anterior descending coronary artery (LAD). Specific high affinity (Kd 0.4 nM) [125I]hCGRP binding sites were localized to the media of both epicardial and myocardial coronary arteries. Binding site density was greater in distal epicardial and myocardial arteries than in proximal epicardial regions of the LAD. Binding sites exhibited a significantly higher affinity for alpha-hCGRP (Ki 1.1 nM) than for hCGRP-(8-37) (Ki 7.0 nM) and [Cys(ACM)2,7]hCGRP (Ki 27.4 nM). Guanosine-5'-O-(3-thiotriphosphate) inhibited [125I]hCGRP binding in a concentration-dependent manner. Extrinsic denervation of the bovine heart resulted in a depletion of CGRP-like immunoreactive perivascular nerve fibres and an increase in the density of coronary artery [125I]hCGRP binding sites (P = 0.0092). The regional distribution of binding sites in human coronary arteries differed from that observed in bovine and porcine vessels. It is concluded that selective, G protein-coupled, CGRP receptors are present in the media of bovine coronary arteries; there are both regional and species differences in the distribution of CGRP binding sites in coronary arteries and endogenous CGRP may exert a tonic influence on coronary vasomotor tone.
采用定量体外放射自显影技术，对牛左前降支冠状动脉（LAD）切片中125I标记的人降钙素基因相关肽（[125I]hCGRP）结合位点进行定位和特性分析。特异性高亲和力（Kd 0.4 nM）的[125I]hCGRP结合位点定位于心外膜和心肌冠状动脉的中膜。LAD远端心外膜和心肌动脉中的结合位点密度高于近端心外膜区域。结合位点对α-hCGRP（Ki 1.1 nM）的亲和力显著高于hCGRP-(8 - 37)（Ki 7.0 nM）和[Cys(ACM)2,7]hCGRP（Ki 27.4 nM）。5'-O-(3-硫代三磷酸)鸟苷以浓度依赖方式抑制[125I]hCGRP结合。牛心脏的外在去神经支配导致降钙素基因相关肽样免疫反应性血管周围神经纤维减少，冠状动脉[125I]hCGRP结合位点密度增加（P = 0.0092）。人冠状动脉中结合位点的区域分布与牛和猪血管中观察到的不同。结论是，牛冠状动脉中膜存在选择性、G蛋白偶联的降钙素基因相关肽受体；冠状动脉中降钙素基因相关肽结合位点的分布存在区域和物种差异，内源性降钙素基因相关肽可能对冠状动脉血管舒缩张力产生紧张性影响。
