An enzymatically stable kyotorphin analog induces pain in subattomol doses

Hiroshi Ueda; Makoto Inoue; Grazyna Weltrowska; Peter W. Schiller

doi:10.1016/S0196-9781(00)00190-X

An enzymatically stable kyotorphin analog induces pain in subattomol doses

Hiroshi Ueda, Makoto Inoue, Grazyna Weltrowska, Peter W. Schiller

Research output: Contribution to journal › Article › peer-review

Abstract

Intraplantar injection of the enzymatically stable, N-methylated kyotorphin analog Tyr(NMe)-Arg-OH produced marked and sharp nociceptive flexor responses in a dose-dependent manner. A significant response was observed with this compound at a dose of 0.01 amol (6000 molecules). Tyr(NMe)-Arg-OH-nociception was completely blocked by the kyotorphin antagonist leucyl-arginine and its enzymatically stable, N-methylated analog, as well as by CP-99994, a specific neurokinin 1 antagonist. These findings suggest that the nociceptive effect produced by Tyr(NMe)-Arg-OH in subattomol doses occurs via specific interaction with the kyotorphin receptor and that the extraordinary potency observed may result from amplification through local substance P release. Copyright (C) 2000 Elsevier Science Inc.

Original language	English (US)
Pages (from-to)	717-722
Number of pages	6
Journal	Peptides
Volume	21
Issue number	5
DOIs	https://doi.org/10.1016/S0196-9781(00)00190-X
State	Published - May 2000
Externally published	Yes

Keywords

Kyotorphin
Kyotorphin analogs
Kyotorphin antagonists
Nociception
Peripheral nociception assay
Subattomol potency
Substance P

ASJC Scopus subject areas

Biochemistry
Physiology
Endocrinology
Cellular and Molecular Neuroscience

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title = "An enzymatically stable kyotorphin analog induces pain in subattomol doses",

abstract = "Intraplantar injection of the enzymatically stable, N-methylated kyotorphin analog Tyr(NMe)-Arg-OH produced marked and sharp nociceptive flexor responses in a dose-dependent manner. A significant response was observed with this compound at a dose of 0.01 amol (6000 molecules). Tyr(NMe)-Arg-OH-nociception was completely blocked by the kyotorphin antagonist leucyl-arginine and its enzymatically stable, N-methylated analog, as well as by CP-99994, a specific neurokinin 1 antagonist. These findings suggest that the nociceptive effect produced by Tyr(NMe)-Arg-OH in subattomol doses occurs via specific interaction with the kyotorphin receptor and that the extraordinary potency observed may result from amplification through local substance P release. Copyright (C) 2000 Elsevier Science Inc.",

keywords = "Kyotorphin, Kyotorphin analogs, Kyotorphin antagonists, Nociception, Peripheral nociception assay, Subattomol potency, Substance P",

author = "Hiroshi Ueda and Makoto Inoue and Grazyna Weltrowska and Schiller, {Peter W.}",

note = "Funding Information: ☆ Parts of this work were supported by Grants-in-Aid from the Ministry of Education, Science, Culture and Sports of Japan, by research grant from The Naito Foundation and Ono Medical Research Foundation, an operating grant from the Medical Research Council of Canada (MT-5655) and an Invitation Fellowship for Research in Japan from the Japan Society for the Promotion of Science to PWS. Copyright: Copyright 2007 Elsevier B.V., All rights reserved.",

year = "2000",

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doi = "10.1016/S0196-9781(00)00190-X",

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AU - Inoue, Makoto

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AU - Schiller, Peter W.

N1 - Funding Information: ☆ Parts of this work were supported by Grants-in-Aid from the Ministry of Education, Science, Culture and Sports of Japan, by research grant from The Naito Foundation and Ono Medical Research Foundation, an operating grant from the Medical Research Council of Canada (MT-5655) and an Invitation Fellowship for Research in Japan from the Japan Society for the Promotion of Science to PWS. Copyright: Copyright 2007 Elsevier B.V., All rights reserved.

PY - 2000/5

Y1 - 2000/5

N2 - Intraplantar injection of the enzymatically stable, N-methylated kyotorphin analog Tyr(NMe)-Arg-OH produced marked and sharp nociceptive flexor responses in a dose-dependent manner. A significant response was observed with this compound at a dose of 0.01 amol (6000 molecules). Tyr(NMe)-Arg-OH-nociception was completely blocked by the kyotorphin antagonist leucyl-arginine and its enzymatically stable, N-methylated analog, as well as by CP-99994, a specific neurokinin 1 antagonist. These findings suggest that the nociceptive effect produced by Tyr(NMe)-Arg-OH in subattomol doses occurs via specific interaction with the kyotorphin receptor and that the extraordinary potency observed may result from amplification through local substance P release. Copyright (C) 2000 Elsevier Science Inc.

AB - Intraplantar injection of the enzymatically stable, N-methylated kyotorphin analog Tyr(NMe)-Arg-OH produced marked and sharp nociceptive flexor responses in a dose-dependent manner. A significant response was observed with this compound at a dose of 0.01 amol (6000 molecules). Tyr(NMe)-Arg-OH-nociception was completely blocked by the kyotorphin antagonist leucyl-arginine and its enzymatically stable, N-methylated analog, as well as by CP-99994, a specific neurokinin 1 antagonist. These findings suggest that the nociceptive effect produced by Tyr(NMe)-Arg-OH in subattomol doses occurs via specific interaction with the kyotorphin receptor and that the extraordinary potency observed may result from amplification through local substance P release. Copyright (C) 2000 Elsevier Science Inc.

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KW - Subattomol potency

KW - Substance P

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An enzymatically stable kyotorphin analog induces pain in subattomol doses

Abstract

Keywords

ASJC Scopus subject areas

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