Ozaki M, Masuda Y, Yamamoto H
Department of Toxicology, Niigata College of Pharmacy, Japan.
J Auton Nerv Syst. 1996 May 6;58(3):147-52. doi: 10.1016/0165-1838(95)00124-7.
The effects of a mixture of peptidase inhibitors, consisting of 100 nM each of amastatin, phosphoramidon, and captopril, on the twitch inhibitory response (0.1 Hz, 0.5 ms duration, maximum intensity) exerted by opioid peptides were investigated. The opioid peptides, Met-enkephalin (50-200 nM), dynorphin(1-13) (0.2-1 nM), and beta h-endorphin (20-100 nM) concentration-dependently inhibited the electrically evoked twitch response. In the presence of the mixture of peptidase inhibitors, the twitch inhibition evoked by Met-enkephalin was significantly increased; however, the twitch inhibition evoked by beta h-endorphin and dynorphin(1-13) was only slightly increased. These increases were abolished by naloxone (NLX; 100 nM). Inhibition of the twitch response (0.1 Hz, 0.5 ms duration, maximum intensity) induced after high frequency stimulation (10 Hz, 0.5 ms pulse width, maximum voltage for various lengths of time) (post-tetanic twitch inhibition) was investigated in isolated guinea pig ileal longitudinal muscles. The mixture of peptidase inhibitors, which did not affect the twitch response or ACh-contraction, increased post-tetanic twitch inhibition. This increase was abolished by naloxone (100 nM). These results suggested that the potentiated post-tetanic twitch inhibition evoked by the peptidase inhibitors in the ileum was due primarily to mu-ligand(s) rather than to the kappa-type of endogenous opioid ligand(s) released from opioidergic neurons.
研究了由氨肽酶抑制剂混合物（其中氨肽菌素、磷酰胺素和卡托普利各100 nM）对阿片肽产生的抽搐抑制反应（0.1 Hz，0.5 ms持续时间，最大强度）的影响。阿片肽，甲硫氨酸脑啡肽（50 - 200 nM）、强啡肽（1 - 13）（0.2 - 1 nM）和β - 内啡肽（20 - 100 nM）呈浓度依赖性抑制电诱发的抽搐反应。在存在肽酶抑制剂混合物的情况下，甲硫氨酸脑啡肽诱发的抽搐抑制作用显著增强；然而，β - 内啡肽和强啡肽（1 - 13）诱发的抽搐抑制作用仅略有增强。这些增强作用被纳洛酮（NLX；100 nM）消除。在离体豚鼠回肠纵行肌中研究了高频刺激（10 Hz，0.5 ms脉冲宽度，不同时长的最大电压）后诱导的抽搐反应（0.1 Hz，0.5 ms持续时间，最大强度）抑制（强直后抽搐抑制）。不影响抽搐反应或乙酰胆碱收缩的肽酶抑制剂混合物增强了强直后抽搐抑制作用。这种增强作用被纳洛酮（100 nM）消除。这些结果表明，肽酶抑制剂在回肠中诱发的增强的强直后抽搐抑制主要归因于μ配体，而非源自阿片能神经元释放的κ型内源性阿片配体。
