title: Hemokinin-1 mediates pruriceptive processing in the rat spinal cord.
abstract: Hemokinin-1 (HK-1) is a new mammalian tachykinin peptide consisting of the amino acid sequence similar to substance P (SP). Although the function of SP, a representative tachykinin peptide, has been well established in the pain system, that of HK-1 has not yet been elucidated. [Leu(11)]-SP had an antagonistic effect on SP-induced scratching behavior, suggesting that [Leu(11)]-HK-1 may also attenuate the induction of scratching behavior by HK-1. Thus, the effects of a pretreatment with [Leu(11)]-HK-1 were evaluated to clarify the function of HK-1. The intrathecal administration of [Leu(11)]-HK-1 attenuated the induction of scratching by HK-1, but not SP, while [Leu(11)]-SP reduced the induction of scratching by SP, but not HK-1. These results indicated that [Leu(11)]-HK-1 may be a more specific antagonist of HK-1-preferred receptors and [Leu(11)]-SP has an antagonistic effect on the SP-preferred receptor, the neurokinin 1 receptor. In the formalin test for examining noxious response, the intrathecal administration of [Leu(11)]-SP, but not [Leu(11)]-HK-1, reduced the number of flinchings and c-Fos-positive cells in the spinal dorsal horn following formalin injection into the plantar region of the hind paw. These results indicated that SP, but not HK-1, is involved in nociceptive processing at the spinal level. To evaluate the involvement of HK-1 and SP in pruritic processing, the effect of [Leu(11)]-HK-1 and [Leu(11)]-SP on the induction of scratching behavior and c-Fos expression by serotonin (5-HT) and histamine was evaluated. The increased induction of scratching behavior and c-Fos expression by 5-HT and histamine was markedly attenuated by pretreatment with both [Leu(11)]-HK-1 and [Leu(11)]-SP, suggesting that HK-1 and SP may be involved in pruritic processing. These results indicate that HK-1 is involved in pruritic processing and [Leu(11)]-HK-1 is a valuable tool for clarifying the mechanisms underlying pruritic processing.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Funahashi
authors.affiliation: Division of Neurobiology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Naono-Nakayama
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ebihara
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Koganemaru
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kuramashi
authors.affiliation: Division of Neurobiology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nishimori
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. Electronic address: ishiday@med.miyazaki-u.ac.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Ishida
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005557:Formaldehyde; D006632:Histamine; D007150:Immunohistochemistry; D008297:Male; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011537:Pruritus / Q000188:drug therapy / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012701:Serotonin; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D015320:Tachykinins; C507968:hemokinin-1; D005557:Formaldehyde; D012701:Serotonin; D013373:Substance P; D006632:Histamine
keywords: [Leu(11)]-hemokinin-1; histamine; pruritus; rat; serotonin; spinal cord