Shinkai M, Tsuruoka H, Wakabayashi S, Yamamoto Y, Takayanagi I
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Jul;350(1):63-7. doi: 10.1007/BF00180012.
Effects of endothelins (ETs) were studied in the rat iris sphincter preparation. Three peptides (ET-1, ET-2 and ET-3) caused contractile responses, and the rank order of agonist potency was: ET-1 = ET-2 > ET-3. The concentration-response curve to ET-1 was shifted to the right by the ETA receptor antagonist cyclo [D-Asp-L-Pro-D-Val-L-Leu-D-Trp] (BQ-123: 10(-7) M), the pA2 value of which was 7.41 +/- 0.09 (n = 4). ET-1 and ET-3, at the concentration of 10(-9) M, potentiated cholinergic contractions evoked by electrical field stimulation (5 and 20 Hz) without affecting the postjunctional sensitivity to carbachol. This potentiating effect was not influenced by BQ-123 (10(-6) M). The ET-evoked percentage increase in the stimulation-induced contraction observed at 5 Hz was significantly greater than that at 20 Hz. A release of immunoreactive ET was detected when the preparation was stimulated at 20 Hz (1.81 +/- 0.36 pg/sphincter n = 6). ET release evoked by 20 Hz stimulation was completely abolished by tetrodotoxin (10(-7) M). In conclusion, ET interacts with two different receptor types, ETA and non-ETA receptors (probably ETB) which exist post- and presynaptically at cholinergic neuroeffector junctions of the rat iris preparation. Stimulation of ETA receptor results in a direct muscle contraction and non-ETA receptor activation facilitates the acetylcholine output from cholinergic nerve endings. It is suggested that ET released from a tetrodotoxin-sensitive site is involved in the modulation of acetylcholine release in the rat iris sphincter preparation.
在内皮素（ETs）对大鼠虹膜括约肌标本的作用研究中，三种肽（ET-1、ET-2和ET-3）均引起收缩反应，激动剂效力的顺序为：ET-1 = ET-2 > ET-3。ET-1的浓度-反应曲线被ETA受体拮抗剂环[D-天冬氨酸-L-脯氨酸-D-缬氨酸-L-亮氨酸-D-色氨酸]（BQ-123：10⁻⁷M）向右移动，其pA2值为7.41±0.09（n = 4）。10⁻⁹M浓度的ET-1和ET-3增强了电场刺激（5和20Hz）诱发的胆碱能收缩，而不影响接头后对卡巴胆碱的敏感性。这种增强作用不受BQ-123（10⁻⁶M）的影响。5Hz时观察到的ET诱发的刺激诱导收缩的百分比增加显著大于20Hz时。当标本以20Hz刺激时，检测到免疫反应性ET的释放（1.81±0.36pg/括约肌，n = 6）。20Hz刺激诱发的ET释放被河豚毒素（10⁻⁷M）完全消除。总之，ET与两种不同的受体类型相互作用，即ETA和非ETA受体（可能是ETB），它们分别存在于大鼠虹膜标本胆碱能神经效应接头的突触后和突触前。刺激ETA受体导致直接的肌肉收缩，而非ETA受体激活促进胆碱能神经末梢的乙酰胆碱释放。提示从河豚毒素敏感部位释放的ET参与了大鼠虹膜括约肌标本中乙酰胆碱释放的调节。
