咯利普兰逆转豚鼠离体气管对沙丁胺醇的耐受性

ROLIPRAM REVERSED SALBUTAMOL TOLERANCE IN GUINEA PIG TRACHEA

本研究目的旨在观察ＰＤＥＩＶ抑制剂咯利普兰对沙丁胺醇（ＳＢ）耐受性的影响。用豚鼠离体气管标本，预先接触ＳＢ１μｍｏｌ·Ｌ－１，１ｈ可使ＳＢ对抗乙酰甲胆碱气管收缩作用的剂量反应曲线右移５倍，最大松弛率下降３０％，形成ＳＢ气管松弛作用的耐受性。磷酸二酯酶（ＰＤＥ）ＩＶ抑制剂咯利普兰能翻转ＳＢ气管松弛作用的耐受性，但ＰＤＥＩＩ抑制剂氰胍哒嗪则不能。虽然蛋白合成抑制剂环己酰亚胺对ＳＢ耐受性无预防作用，但上述结果仍提示ＳＢ气管松弛作用的耐受性可能与ＰＤＥＩＶ活性的增高有关。

Studies were carried out to examine the role of phosphodiesterase(PDE) III and PDE IV in the development of tachyphylaxis of isolated guinea pig trachea to β 2 adrenoceptor agonists. Treating trachea with salbutamol(SB) 1 μmol·L -1 for 1 h produced a 5 fold rightward shift of the SB concentration response curve for the spasmolytic effect against methacholine induced bronchocon traction and decreased the maximum SB induced relaxation by 30%, i.e. induced tolerance of airway response of SB in vitro . The PDE IV inhibitor rolipram (Rol, 1 μmol·L -1 , IC 50 ), but not the PDE III inhibitor siguazodan (SK&F 94836, 1 μmol·L -1 , IC 50 ), reversed the SB tolerance. However, the protein synthesis inhibitor cycloheximide(10 μmol·L -1 ) did not abolish the SB tolerance. These results indicate that the SB tolerance may be related to increase in PDE IV activity.