- 期刊
- OpenAccess
內皮素受體拮抗劑
Endothelin Receptor Antagonists
摘要
內皮素（endothelin; ET）是由21個胺基酸組成的內生強力血管收縮肽，可能與人許多疾病有關，其分子內含兩個二硫化鍵（disulfide bond）。內皮素最初是由內皮細胞分離出，目前已知有三種內皮素：ET-1、ET-2及ET-3。ET-1會引起明顯的血管收縮等多種生理活性；ET-2並無特殊生理功能。內皮素受體亦分三種：ET(subscript A)、ET(subscript B)及ET(subscript C)。ET(subscript A)主要存在於血管平滑肌，對ET-1具有高選擇性。ET-1與ET(subscript A)結合後，引起強力血管收縮。ET(subscript B)與ET-1、ET-2、ET-3的親力相近，故不具選擇性。內皮素受體抗拮劑具仿內皮素與受體結合的主要立體結構點，使內皮素無法與受體結合，而產生拮抗作用。內皮素受體拮抗劑依化學結構，區分為兩大類：（一）肽化合物；（二）非肽分子。前者係含藥效基團的小分子肽；後者再分為蒽醌（anthraquinones），asterric acids, myricerone caffeoyl esters, N-嘧啶苯磺胺（N-pyrimidinylbenzenesulfonamides），N-異噁唑萘磺胺（N-isoxalylnaphthalenesulfonamides），二氫吡啶酐（dihydropyridine anhydrides），及氫茚羥酸（indanecarboxylic acids）等。其中屬N-嘧啶苯磺胺結構之ET(subscript A)強力競爭拮抗劑bosentan(11)，是唯一進行臨床試驗的內皮素受體拮抗劑。內皮素受體拮抗劑對某些高血壓及急性腎衰竭等特定的動物疾病模式有效，但這類化合物在人體的療效，仍有待臨床評估。內皮素受體拮抗劑的快速發展，將使吾人進一步瞭解內皮素在病態生理學的角色，及其受體拮抗劑在臨床治療上的意義。
並列摘要
Endothelin (ET), which is implicated in several human disease states including hypertension, congestive heart failure, pulmonary hypertension, ischemia, and cerebral vasospasm, is one of the most potent known vasoconstrictor peptides released from endothelial cells and has attracted tremendous interest as a possible target for therapeutic intervention. The ET family of 21-amino acid peptides (ET-1, ET-2, and ET-3) possess an unusual chemical structure containing two disulfide bonds. The ET receptors are differentiated by their relative affinities for the three isopeptides and designated ET(subscript A) (ET-1＞ET-3), ET(subscript B) (ET-1=ET-3), and ET(subscript C) (ET-3＞ET-1), respectively. In this Review some of the biological actions of the ET's and their possible mechanisms of action were described. The final sections of this article discussed the recently reported ET receptor antagonists and their potential therapeutic applications.