A Dose-Response Study of Anticholinesterase Drugs on Contractile and Phosphatidylinositol Responses of Rat Trachea
A Dose-Response Study of Anticholinesterase Drugs on Contractile and Phosphatidylinositol Responses of Rat Trachea
复制标题
抗胆碱酯酶药物对大鼠气管收缩和磷脂酰肌醇反应的剂量反应研究
DOI：
10.1097/00000539-200101000-00020
复制
发表时间：
2001
影响因子：
5.7
通讯作者：
K. Sumikawa
中科院分区：
文献类型：
--
作者：
A. Tsuda;O. Shibata;M. Saito;Shigeru Hashimoto;Shunichiro Iwanaga;T. Makita;K. Sumikawa
我们研究了大剂量的抗胆碱酯酶药物是否会抑制气道平滑肌的毒蕈碱受体。使用大鼠气管环或切片进行等长张力和形成的[3H]肌醇单磷酸(IP1)的体外测量。新斯的明和吡斯的明在小剂量（分别为10μM和≤100μM）时引起肌肉收缩和IP1积累，但在较大剂量（1000μM）时减弱肌肉收缩和IP1积累。依酚铵不影响平滑肌张力和IP1水平。当大剂量 (1000 µM) 给药时，新斯的明、吡斯的明和依酚铵可减弱卡巴胆碱 (5.5 µM) 诱导的平滑肌收缩和 IP1 积聚。大剂量新斯的明引起的收缩减弱不受甲曲胺（一种 M2 毒蕈碱受体拮抗剂）的影响，但通过用新鲜的 Krebs-Henseleit 溶液洗涤可以逆转。结果表明，抗胆碱酯酶药物对大鼠气管的张力和磷脂酰肌醇反应具有双重作用。大剂量抗胆碱酯酶药物会导致气道平滑肌松弛，这种情况可能见于接受过量抗胆碱酯酶治疗的重症肌无力患者。含义 新斯的明和吡斯的明对大鼠气管的张力和磷脂酰肌醇反应具有双重作用，但依酚铵则不然。大剂量抗胆碱酯酶药物会导致气道平滑肌松弛，这种情况可能见于接受过量抗胆碱酯酶治疗的重症肌无力患者。
We investigated whether anticholinesterase drugs in large doses inhibit muscarinic receptors of airway smooth muscle. In vitro measurements of isometric tension and [3H]inositol monophosphate (IP1) that formed were conducted by using rat tracheal rings or slices. Neostigmine and pyridostigmine caused muscular contraction and IP1 accumulation in small doses (10 &mgr;M and ≤100 &mgr;M, respectively), but they attenuated muscular contraction and IP1 accumulation in larger doses (1000 &mgr;M). Edrophonium did not affect the smooth muscle tone and IP1 levels. Neostigmine, pyridostigmine, and edrophonium attenuated the carbachol (5.5 &mgr;M)-induced smooth muscle contraction and IP1 accumulation, when administered in large doses (1000 &mgr;M). The attenuation of contraction by neostigmine at large doses was not affected by methoctramine, an M2 muscarinic receptor antagonist, but was reversed by washing with fresh Krebs-Henseleit solution. The results suggest that anticholinesterase drugs have dual effects on the tension and phosphatidylinositol responses of rat trachea. Large doses of anticholinesterase drugs cause airway smooth muscle relaxation, which may be seen in patients with myasthenia gravis who have received excessive anticholinesterase therapy. Implications Neostigmine and pyridostigmine, but not edrophonium, have dual effects on the tension and phosphatidylinositol responses of rat trachea. Large doses of anticholinesterase drugs cause airway smooth muscle relaxation, which may be seen in patients with myasthenia gravis who have received excessive anticholinesterase therapy.
m1、m2 和 m3 毒蕈碱受体亚型的变构相互作用。
DOI：
--
发表时间：
1991
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Lee,NH;el-Fakahany,EE
通讯作者：
el-Fakahany,EE
内源性一氧化氮抑制豚鼠吸入冷空气引起的支气管收缩：激肽的作用。
DOI：
10.1164/ajrccm.157.2.9704074
发表时间：
1998
期刊：
American journal of respiratory and critical care medicine.
影响因子：
--
作者：
Yoshihara,S;Nadel,JA;Figini,M;Emanueli,C;Pradelles,P;Geppetti,P
通讯作者：
Geppetti,P