Chaytor A T, Martin P E, Edwards D H, Griffith T M
Department of Diagnostic Radiology, Wales Heart Research Institute, University of Wales College of Medicine, Cardiff CF14 4XN, United Kingdom.
Am J Physiol Heart Circ Physiol. 2001 Jun;280(6):H2441-50. doi: 10.1152/ajpheart.2001.280.6.H2441.
Synthetic peptides homologous to the Gap 26 and Gap 27 domains of the first and second extracellular loops of the major vascular connexins (Cx37, Cx40, and Cx43) have been used to investigate the role of gap junctions in endothelium-derived hyperpolarizing factor (EDHF)-type relaxations of the rat hepatic artery. These peptides were designated 37,40Gap 26, 43Gap 26, 37,43Gap 27, and 40Gap 27, according to connexin specificity. When administered at 600 microM, none of the peptides individually affected maximal EDHF-type relaxations to ACh. By contrast, at 300 microM each, paired peptide combinations targeting more than one connexin subtype attenuated relaxation by up to 50%, and responses were abolished by the triple peptide combination 43Gap 26 + 40Gap 27 + 37,43Gap 27. In parallel experiments with A7r5 cells expressing Cx40 and Cx43, neither 43Gap 26 nor 40Gap 27 affected intercellular diffusion of Lucifer yellow individually but, in combination, significantly attenuated dye transfer. The findings confirm that functional cell-cell coupling may depend on more than one connexin subtype and demonstrate that direct intercellular communication via gap junctions constructed from Cx37, Cx40, and Cx43 underpins EDHF-type responses in the rat hepatic artery.
与主要血管连接蛋白（Cx37、Cx40和Cx43）第一和第二细胞外环的Gap 26和Gap 27结构域同源的合成肽已被用于研究缝隙连接在大鼠肝动脉内皮衍生超极化因子（EDHF）型舒张中的作用。根据连接蛋白特异性，这些肽分别命名为37,40Gap 26、43Gap 26、37,43Gap 27和40Gap 27。当以600微摩尔的浓度给药时，这些肽单独使用均不影响对乙酰胆碱（ACh）的最大EDHF型舒张反应。相比之下，当每种肽以300微摩尔的浓度使用时，针对不止一种连接蛋白亚型的配对肽组合可使舒张反应减弱多达50%，并且三联肽组合43Gap 26 + 40Gap 27 + 37,43Gap 27可消除反应。在对表达Cx40和Cx43的A7r5细胞进行的平行实验中，43Gap 26和40Gap 27单独使用时均不影响荧光素黄的细胞间扩散，但联合使用时可显著减弱染料转移。这些发现证实功能性细胞间偶联可能取决于不止一种连接蛋白亚型，并表明通过由Cx37、Cx40和Cx43构建的缝隙连接进行的直接细胞间通讯是大鼠肝动脉中EDHF型反应的基础。
