Abela A P, Daniel E E
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Am J Physiol. 1995 Jan;268(1 Pt 1):L47-55. doi: 10.1152/ajplung.1995.268.1.L47.
In canine bronchi bathed in 10(-6) M indomethacin (IDM), prostaglandin (PG) E2 inhibited electrical field stimulation (EFS)- and acetylcholine (ACh)-mediated contractions and excitatory junction potentials (EJP) in a concentration-dependent manner without altering the resting membrane potential. EFS-induced EJPs were abolished at 10(-7) M PGE2, which shifted responses to ACh 10-fold rightward. Thus PGE2 predominantly inhibited the release of ACh and secondarily decreased smooth muscle response to ACh. U-46619, an analogue of thromboxane A2 (TxA2), initiated tetrodotoxin- and atropine-insensitive contractions in a concentration-dependent manner. U-46619 (10(-9) M) did not alter significantly EFS- or ACh-stimulated contractions and potentiated EFS amplitude of EJPs without depolarizing muscle cells. Either prejunctional activation of ACh release by TxA2 or postjunctional potentiation of the response to ACh can explain these findings. U-46619 (> or = 10(-8) M) depolarized the membrane potential, initiating oscillations accompanied by a large contraction. Addition of 10(-8) M nitrendipine, but not tetraethylammonium (25 mM), blocked the oscillations selectively. Other prostanoids (PGD2, PGI2, and PGF2 alpha) had no significant effects on canine bronchi. In the absence of IDM, PGE2 accumulated, EFS contractions decreased with time, and EJPs disappeared. We conclude that in canine bronchi PGE2 predominantly inhibits ACh release and endogenous PGE2 acts similarly, whereas TxA2 excites, probably at postjunctional sites.
在浸浴于10⁻⁶ M消炎痛（IDM）的犬支气管中，前列腺素（PG）E₂以浓度依赖性方式抑制电场刺激（EFS）和乙酰胆碱（ACh）介导的收缩以及兴奋性接头电位（EJP），而不改变静息膜电位。在10⁻⁷ M PGE₂时，EFS诱导的EJP被消除，这使对ACh的反应向右移动了10倍。因此，PGE₂主要抑制ACh的释放，其次降低平滑肌对ACh的反应。血栓素A₂（TxA₂）的类似物U-46619以浓度依赖性方式引发对河豚毒素和阿托品不敏感的收缩。U-46619（10⁻⁹ M）对EFS或ACh刺激的收缩没有显著影响，并且在不使肌肉细胞去极化的情况下增强了EJP的EFS幅度。TxA₂对ACh释放的接头前激活或对ACh反应的接头后增强都可以解释这些发现。U-46619（≥10⁻⁸ M）使膜电位去极化，引发振荡并伴有大的收缩。加入10⁻⁸ M尼群地平而非四乙铵（25 mM）可选择性地阻断振荡。其他前列腺素（PGD₂、PGI₂和PGF₂α）对犬支气管没有显著影响。在没有IDM的情况下，PGE₂积累，EFS收缩随时间减少，EJP消失。我们得出结论，在犬支气管中，PGE₂主要抑制ACh释放，内源性PGE₂的作用类似，而TxA₂可能在接头后部位起兴奋作用。
