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Dynorphin-(1-13), an extraordinarily potent opioid peptide

Goldstein, Avram and Tachibana, S. and Lowney, L. I. and Hunkapiller, M. and Hood, L. (1979) Dynorphin-(1-13), an extraordinarily potent opioid peptide. Proceedings of the National Academy of Sciences of the United States of America, 76 (12). pp. 6666-6670. ISSN 0027-8424. PMCID PMC411929.

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We describe the opioid properties of a tridecapeptide, the sequence of which corresponds to the NH2-terminal sequence of dynorphin, a novel porcine pituitary endorphin. It contains [Leu]enkephalin. In the guinea pig ileum longitudinal muscle preparation it is about 700 times more potent than [Leu]enkephalin. Its effects in this tissue are blocked completely by naloxone, but the apparent affinity of naloxone is 1/13th that for blockade of [Leu]enkephalin or normorphine. In the mouse vas deferens, this peptide is 3 times more potent than [Leu]enkephalin. Well-washed rat brain membranes degrade the peptide rapidly, suggesting the presence of a membrane-bound degradative enzyme. The peptide displays considerable immunoreactivity in assays with antisera that have been used for the immunohistochemical localization of [Leu]enkephalin. The remarkable enhancement of the potency of [Leu]enkephalin by the COOH-terminal extension -Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-OH suggests new interpretations concerning the structure of opiate receptors and the function of the enkephalin pentapeptides.

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Hood, L.0000-0001-7158-3678
Additional Information:© 1979 by the National Academy of Sciences. Communicated by Floyd E. Bloom, September 7, 1979. None of this work could have been done without the cooperation of Dr. J.D. Fisher (Armour Pharmaceuticals, Kankakee, IL) whose foresight was responsible for stockpiling byproducts of commercial pituitary hormone production and who furnished the melanotropin concentrate that was our starting material. Drs. Stanley Watson and Richard J. Miller kindly supplied samples of their [Leu]enkephalin antisera. Asha Naidu provided technical assistance of the highest quality throughout this project. We thank Dr. Maureen Ross and Fanny Liu for the radioimmunoassays, Dr. Barbara Herman and Clarence Omoto for their participation in the preliminary behavioral experiments, Dr. Vartan Ghazarossian and Keiko Otsu for the degradation studies, Patricia Lowery for some of the assays, and Dr. Brian M. Cox for helpful comment and criticism. The work was supported by Grant DA-1199 from the National Institute on Drug Abuse and Grant GM-06965 from the National Institutes of Health.
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Subject Keywords:endorphin; [Leu]enkephalin; pituitary; neuropeptide; endogenous morphine-like peptide
Issue or Number:12
PubMed Central ID:PMC411929
Record Number:CaltechAUTHORS:GOLpnas79
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13226
Deposited By: Tony Diaz
Deposited On:09 Feb 2009 22:58
Last Modified:03 Oct 2019 00:35

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