title: An amino-terminal fragment of hemokinin-1 has an inhibitory effect on pruritic processing in rats.
abstract: Hemokinin-1 (HK-1) is a peptide encoded by the preprotachykinin gene, TAC-4, and shares the hydrophobic carboxyl-terminal (C-terminal) region common to mammalian tachykinin peptides, such as substance P (SP). It is generally believed that C-terminal fragments of SP elicit an excitatory effect, while pretreatment with amino-terminal (N-terminal) fragments of SP inhibits the function of SP; however, there is no available information on HK-1. Therefore, to clarify the characteristics of C-terminal and N-terminal fragments of HK-1, HK-1 was divided into HK-1 (1-5) as the N-terminal fragment and HK-1 (6-11) as the C-terminal fragment based on the similarity of amino acids between HK-1 and SP. Intrathecal administration of HK-1 (6-11) induced scratching behavior similar to HK-1, while HK-1 (1-5) hardly induced scratching. Pretreatment with HK-1 (1-5), however, attenuated scratching induced by HK-1 and SP, whereas pretreatment with SP (1-5) attenuated SP-induced scratching, but not HK-1. Furthermore, intrathecal administration of HK-1 (1-5) and SP (1-5) markedly attenuated the induction of flinching and enhancement of c-Fos expression in the spinal cord following the intradermal administration of formalin, a noxious stimulant, while pretreatment with HK-1 (1-5), but not SP (1-5), markedly attenuated the induction of scratching behavior by subcutaneous administration of pruritic agents, such as serotonin or histamine. Taken together, these findings indicate that HK-1 (1-5) suppresses pruritic and nociceptive processing, while SP (1-5) suppresses nociceptive processing. Therefore, it is suggested that HK-1 (1-5) may be a useful tool for revealing pruritic processing and HK-1 may play a crucial role in pruritic processing.
authors.affiliation: Division of Neurobiology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan; Department of Neuroscience, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. Electronic address: rumi_n-n@med.miyazaki-u.ac.jp.
authors.forename: R
authors.initials: R
authors.lastname: Naono-Nakayama
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 Environmental Information, Faculty of Environmental Studies, Hiroshima Institute of Technology, 2-1-1, Miyake, Saeki-ku, Hiroshima 731-5193, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Matsushima
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sameshima
authors.affiliation: Department of Neuroscience, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takamiya
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: T
authors.initials: T
authors.lastname: Nishimori
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D007278:Injections, Spinal; D008297:Male; D010147:Pain Measurement; D010446:Peptide Fragments / Q000633:toxicity*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011537:Pruritus / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000009:adverse effects; D015320:Tachykinins / Q000009:adverse effects / Q000737:chemistry*; D013997:Time Factors
chemical_list: D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D015320:Tachykinins; C507968:hemokinin-1; D013373:Substance P
keywords: 5-HT; 5-hydoroxytryptamine; HK-1; NK1; SP; amino-terminal fragment; hemokinin-1; neurokinin 1; nociception; pruritus; scratching; spinal cord; substance P