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Dynorphin-(1-13), an extraordinarily potent opioid peptide.
Open accessAbstract
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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“This system is comprised of three types of opioid receptors: μ (MOR), δ (DOR), and κ (KOR); and their endogenous ligands, endorphin, enkephalin and dynorphin (Hughes et al 1975; Birdsall and Hulme 1976; Goldstein et al 1979; Evans et al 1992; Kieffer et al 1992; Chen et al 1993; Yasuda et al 1993).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Goldstein et al 1979
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“The ability to produce dynorphin and analogues by solid-phase peptide synthesis (Goldstein, et al., 1979) opened the way to a wide range of structure-activity relationship studies on various peptide structures.”
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“In the 1970s, DOR-selective enkephalins [12], KOR-selective dynorphins [13,14], and non-selective β -endorphins [15] were isolated from the mammalian brain.”
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The next frontier in the molecular biology of the opioid system
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Central Neurotransmitters and Acupuncture Analgesia
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‘Dynorphin’ in plasma: enzymatic artifact and authentic immunoreactivity
Howlett, T. A., Walker, J. D., BESSER, G. M., & REES, L. H. (1984) · Regulatory Peptides · doi:10.1016/0167-0115(84)90168-x · Cited by 15
Schmidhammer, H., Erli, F., Guerrieri, E., & Spetea, M. (2020) · Molecules · doi:10.3390/molecules25215092 · Cited by 14
“The endogenous kappa opioid system comprises the KOR and endogenous peptide ligands, the dynorphins, named after the Greek word dynamis (power) [18].”
BackgroundBhargava, H. N., Matwyshyn, G. A., & Ramarao, P. (1991) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(91)90002-n · Cited by 14
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Fraction I Endorphin in Cerebrospinal Fluid Clinical Studies
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The opioid receptor: emergence through millennia of pharmaceutical sciences
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A review of the kappa opioid receptor system in opioid use
Çayır, S., Zhornitsky, S., Barzegary, A., Carreño, E. S., Sarfo-Ansah, W., Funaro, M. C., Matuskey, D., & Angarita, G. A. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105713 · Cited by 15
“In addition, although dynorphin is considered the naturally occurring ligand for the KOR (Goldstein et al., 1979), it is not highly selective and has MOR agonist activity (James and Goldstein, 1984; Zhou et al., 2015).”
BackgroundOpioid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
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Biochemical and Genetic Studies of Tourette’s Syndrome
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β-Endorphin: Synthetic Analogs and Structure-Activity Relationships
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Regional interactions of opioid peptides at μ and δ sites in rat brain
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Metadata
- Authors
- Goldstein, A., Tachibana, S., Lowney, L. I., Hunkapiller, M., & Hood, L.
- Affiliations
- California Institute of Technology (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1979-12
- Volume
- 76
- Issue
- 12
- Pages
- 6666-6670
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC411929
- OpenAlex
- W2033680879
- Cited by
- 882
- References
- 18
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 8 · 2023: 14 · 2022: 10 · 2021: 14 · 2020: 23 · 2019: 13 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 8 · 2014: 16 · 2013: 23 · 2012: 18
- FWCI
- 24.93
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Keywords
- dynorphin A(1-13), opioid peptides, leu-enkephalin, enkephalin, naloxone, opioid receptors, vas deferens, peptide degradation, immunoreactivity
- MeSH terms
- Amino Acid Sequence, Animals, Biological Assay, Dose-Response Relationship, Drug, Endorphins, Guinea Pigs, Ileum, Radioligand Assay, Receptors, Opioid, Structure-Activity Relationship, Swine, Rats
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