普罗托品松弛气管平滑肌的作用机制研究

目的　为评价普罗托品 (Pro)作为平喘药侯选者的可能性提供资料。方法　①观察不同浓度Pro对组胺、乙酰胆碱收缩的豚鼠离体气管螺旋条的舒张作用及其量效反应。②放射免疫法测定Pro对家兔气管平滑肌中环腺苷酸 (cAMP)、环鸟苷酸(cGMP)水平的影响。③高效液相色谱法检测Pro对豚鼠气管平滑肌磷酸二酯酶 (PDE)活性的影响。结果　①Pro能明显抑制组胺和乙酰胆碱引起的豚鼠离体气管条收缩 ,使其量效曲线右移 ,最大反应压低 ,pD2 ′分别为 3.11和 3.4 5。②Pro能增加家兔气管平滑肌中cAMP水平 ,而cGMP水平的变化无统计学意义。③Pro能抑制水解cAMP的PDE活性 ,但水解cGMP的PDE活性无明显降低。结论　Pro可抑制豚鼠气管平滑肌的收缩 ,其作用机制之一可能为其抑制气管平滑肌PDE活性 ,主要通过提高细胞中cAMP水平 ,进而松弛气管平滑肌

Effects of protopine on tracheal smooth muscle and its mechanism

AIM To provide information for evaluating the possibility that protopine(Pro) could be a candidate of anti-asthma agents. METHODS In vitro effects of Pro on the concentration-response curves of guinea pig tracheal spiral strips for histamine and acetylcholine were observed. ② The contents of cAMP and cGMP in rabbit′s tracheal smooth muscle affected by Pro were determined by radioimmunoassay. ③ The phosphodiesterase(PDE) activities in guinea pig trachealis affected by Pro was assayed with reversed-phase high performance liquid chromatography. RESULTS ① Pro markedly depressed the constriction of guinea pig tracheal spiral strips induced by histamine or acetylcholine, and shifted the concentration-response curves to right. The maximal responses were significantly depressed, showing a non-competitive antagonism. The pD₂′of Pro for constrictions induced by histamine and acetylcholine were 3.11 and 3.45, respectively. ② Pro increased cAMP levels in rabbit tracheal smooth muscles, but had no significant increase in their cGMP level. ③ Pro inhibited the cAMP-PDE activities in guinea pig tracheal smooth muscles, but had no significant decrease in their cGMP-PDE activities. CONCLUSION Pro can inhibit the constriction of tracheal smooth muscle. One of its mechanisms may be the increasing effect of Pro on cAMP levels by inhibiting the cyclic nucleotide PDE activities in trachea, then relaxing the tracheal smooth muscle.