title: Preliminary analgesic properties of deltorphin-5-methoxytryptamine chimeric opioid peptides.
abstract: To further understand the relationship between melatonin (MT) and deltorphins (Dels) in pain modulation, two chimeric peptides (Del I-5-methoxytryptamine and Del II-5-methoxytryptamine) both containing 5-methoxytryptamine at the carboxyl-terminal of Dels mimicking MT were designed, synthesized and characterized by tail-flick assay in mice. Results showed that intracerebroventricular (i.c.v.) administration of Del I-5-methoxytryptamine (YaFDVVG-X, X is 5-methoxytryptamine, 5, 50 nmol/kg) or Del II-5-methoxytryptamine (YaFEVVG-X, X is 5-methoxytryptamine, 5, 50 nmol/kg) produced stronger analgesia than deltorphins (Del I or Del II alone), and acting even longer and stronger than cocktails containing Del I or Del II (50 nmol/kg) and MT (50 nmol/kg). Naloxone (i.p., 100 nmol/kg) could totally block the analgesic effects induced by the chimeric peptides, while luzindole (specific antagonist of melatonin receptor, i.p., 250 nmol/kg) could only partially inhibit the effects down to that induced by Dels alone. Interestingly, Del I-5-methoxytryptamine and Del II-5-methoxytryptamine act weaker with δ receptor than Dels in vitro but could induce much longer analgesia through co-activating δ opioid receptor and melatonin receptor.
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, 222 Tianshui South Road, Lanzhou 730000, Gansu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Meixing
authors.initials: M
authors.lastname: Li
authors.forename: Qiaoying
authors.initials: Q
authors.lastname: Jin
authors.forename: Shouliang
authors.initials: S
authors.lastname: Dong
mesh_terms: D008735:5-Methoxytryptamine / Q000737:chemistry*; D000700:Analgesics / Q000737:chemistry* / Q000627:therapeutic use*; D000818:Animals; D008297:Male; D008550:Melatonin / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry*; D018847:Opioid Peptides / Q000737:chemistry* / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy
chemical_list: D000700:Analgesics; D009842:Oligopeptides; D018847:Opioid Peptides; C059567:deltorphin; D008735:5-Methoxytryptamine; D008550:Melatonin