Structure-activity relationships of naturally occurring and synthetic opioid tetrapeptides acting on locus coeruleus neurons

Y. R. Yang, T. H. Chiu*, C. L. Chen

*此作品的通信作者

研究成果: Article同行評審

35 引文 斯高帕斯(Scopus)

摘要

Intracellular recording was used to study the effects of eight opioid tetrapeptides with similar amino acid sequences, namely endomorphin-1 (Tyr-Pro-Trp-Phe-NH2), endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), morphiceptin (Tyr-Pro-Phe-Pro-NH2), hemorphin-4 (Tyr-Pro-Trp-Thr), Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2), TAPS (Tyr-d-Arg-Phe-Sar) and DALDA (Tyr-d-Arg-Phe-Lys-NH2), on neurons of the rat locus coeruleus, using a submerged brain slice preparation. All the tetrapeptides inhibited the spontaneous firing of all neurons of the locus coeruleus tested. Higher concentrations also caused hyperpolarization of the neurons and a reduction in input resistance. These inhibitory effects were rapidly and completely reversed by CTAP (d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2, a selective μ-opioid receptor antagonist). The IC50 of the opioid tetrapeptides, in terms of inhibition of spontaneous firing of locus coeruleus neurons, as compared to the concentrations which produced a 5-mV hyperpolarization (HC(5 mV)) were calculated, giving the same rank order of potency: TAPS (IC50=1.9 nM, HC(5 mV)=3.4 nM)>endomorphin-1 (IC50=8.8 nM, HC(5 mV)=22.1 nM) and endomorphin-2 (IC50=5.3 nM, HC(5 mV)=16.1 nM)>DALDA (IC50=20 nM, HC(5 mV)=143 nM)>morphiceptin (IC50=65 nM, HC(5 mV)=335 nM)>Tyr-W-MIF-1 (IC50=3.8 μM, HC(5 mV)=6.7 μM)>hemorphin-4 (IC50=6.7 μM, HC(5 mV)=36.9 μM)>Tyr-MIF-1 (IC50=37.5 μM, HC(5 mV)=76.2 μM). Comparison of the ability of endomorphin-1 and endomorphin-2 to inhibit spontaneous firing based on single-cell recordings (n=5) showed these two peptides to be equipotent. Based on these results, the structure-activity relationships of these opioid tetrapeptides are discussed herein. Copyright (C) 1999 Elsevier Science B.V.

原文English
頁(從 - 到)229-236
頁數8
期刊European Journal of Pharmacology
372
發行號3
DOIs
出版狀態Published - 1999

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