Ishikawa H, Yoshitomi T, Harada Y, Katori M, Ishikawa S
Department of Ophthalmology, Kitasato University School of Medicine, Kanagawa, Japan.
Curr Eye Res. 1993 Dec;12(12):1049-55. doi: 10.3109/02713689309033502.
The contractile activity of endothelins (ETs) and their effect on twitch contraction evoked by electrical field stimulation were studied in the isolated rabbit iris sphincter and dilator muscles using the isometric tension recording method. ET-1, ET-2 and ET-3 caused slow contractile response of the sphincter as well as the dilator muscles, with sphincter muscle EC50 values of 37.3, 58.0 and 84.3 nM, and dilator muscle values of 31.7, 69.0 and 224.4 nM, respectively. These contractile responses were not affected by atropine (1 microM), prazosin (1 microM) or indomethacin (1 microM). ET-1 and ET-3 slightly but significantly inhibited the fast cholinergic component of twitch contraction of the sphincter muscle evoked by field stimulation, without affecting the response to carbachol. However, ET-1 did not affect the slow substance P-ergic component of twitch contraction of this preparation. In the dilator muscle, ET-1 and ET-3 had little effect on the contraction induced by phenylephrine but reduced the amplitude of the twitch contraction evoked by the field stimulation. The inhibitory effect of ETs on the dilator muscle was antagonized by pretreatment with BQ-123 (100 nM), which is a selective ETA receptor antagonist. Pretreatment with indomethacin (1 microM) also attenuated the inhibitory effect of ETs on the twitch contraction. These results suggest that ETs may have two sites of action, pre- and post-synaptic effects, on the rabbit iris sphincter muscle as well as the dilator muscle. All three ET isopeptides may have direct contractile activity on the smooth muscles of the sphincter as well as the dilator without mediation by prostaglandins or neuronal mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
采用等长张力记录法，在离体兔虹膜括约肌和开大肌中研究了内皮素（ETs）的收缩活性及其对电场刺激诱发的抽搐收缩的影响。ET-1、ET-2和ET-3引起括约肌以及开大肌的缓慢收缩反应，括约肌肌肉的EC50值分别为37.3、58.0和84.3 nM，开大肌肌肉的EC50值分别为31.7、69.0和224.4 nM。这些收缩反应不受阿托品（1 microM）、哌唑嗪（1 microM）或吲哚美辛（1 microM）的影响。ET-1和ET-3轻微但显著抑制电场刺激诱发的括约肌肌肉抽搐收缩的快速胆碱能成分，而不影响对卡巴胆碱的反应。然而，ET-1不影响该制剂抽搐收缩的缓慢P物质能成分。在开大肌中，ET-1和ET-3对去氧肾上腺素诱导的收缩影响很小，但降低了电场刺激诱发的抽搐收缩幅度。ETs对开大肌的抑制作用可被选择性ETA受体拮抗剂BQ-123（100 nM）预处理所拮抗。吲哚美辛（1 microM）预处理也减弱了ETs对抽搐收缩的抑制作用。这些结果表明，ETs可能在兔虹膜括约肌和开大肌上有两个作用位点，即突触前和突触后效应。所有三种ET同工肽可能对括约肌和平滑肌有直接收缩活性，而无需前列腺素或神经元机制介导。（摘要截短于250字）
