title: Neuropeptide glutamic acid-isoleucine (NEI)-induced paradoxical sleep in rats.
abstract: Neuropeptideglutamic acid-isoleucine (NEI) as well as melanin concentrating hormone (MCH) is cleaved from the 165 amino acid protein, prepro-melanin concentrating hormone (prepro-MCH). Among many physiological roles of MCH, we demonstrated that intracerebroventricular (icv) injection of MCH induced increases in REM sleep episodes as well as in non REM sleep episodes. However, there are no studies on the effect of NEI on the sleep-wake cycle. As for the sites of action of MCH for induction of REM sleep, the ventrolateral periaqueductal gray (vlPAG) has been reported to be one of its site of action. Although MCH neurons contain NEI, GABA, MCH, and other neuropeptides, we do not know which transmitter(s) might induce REM sleep by acting on the vlPAG. Thus, we first examined the effect of icv injection of NEI on the sleep-wake cycle, and investigated how microinjection of either NEI, MCH, or GABA into the vlPAG affected REM sleep in rats. Icv injection of NEI (0.61μg/5μl: n=7) significantly increased the time spent in REM episodes compared to control (saline: 5μl; n=6). Microinjection of either NEI (61ng/0.2μl: n=7), MCH (100ng/0.2μl: n=6) or GABA (250mM/0.2μl: n=7) into the vlPAG significantly increased the time spent in REM episodes and the AUC. Precise hourly analysis of REM sleep also revealed that after those microinjections, NEI and MCH increased REM episodes at the latter phase, compared to GABA which increased REM episodes at the earlier phase. This result suggests that NEI and MCH may induce sustained REM sleep, while GABA may initiate REM sleep. In conclusion, our findings demonstrate that NEI, a cleaved peptide from the same precursor, prepro-MCH, as MCH, induce REM sleep at least in part through acting on the vlPAG.
authors.affiliation: Department of Anesthesiology, Teikyo University School of Medicine, Japan. Electronic address: fujimoto@med.teikyo-u.ac.jp.
authors.forename: Moe
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Anesthesiology, Showa University School of Medicine, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Department of Anesthesiology, Teikyo University School of Medicine, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Department of Anesthesiology, Teikyo University School of Medicine, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Takata
authors.affiliation: Department of Anesthesiology, Teikyo University School of Medicine, Japan.
authors.forename: Shigehito
authors.initials: S
authors.lastname: Sawamura
mesh_terms: D000818:Animals; D018698:Glutamic Acid / Q000008:administration & dosage / Q000378:metabolism; D007028:Hypothalamic Hormones / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D007532:Isoleucine / Q000008:administration & dosage / Q000378:metabolism; D008543:Melanins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000008:administration & dosage* / Q000378:metabolism; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010907:Pituitary Hormones / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage
chemical_list: D007028:Hypothalamic Hormones; D008543:Melanins; D009479:Neuropeptides; D010907:Pituitary Hormones; D007532:Isoleucine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C019463:melanin-concentrating hormone
keywords: Gamma aminobutyric acid; Lateral periaqueductal gray; Melanin concentrating hormone; Neuropeptide glutamic acid-isoleucine