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Cited by 63Neuropeptides and Animal PhysiologyPain Mechanisms and TreatmentsIon Channels and Receptors

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Activation of kappa opioid receptors by U50488H and morphine enhances the release of substance P from rat trigeminal nucleus slices

Suarez-Roca, H, Maixner, W·1993·The Journal of Pharmacology and Experimental Therapeutics
DOI 10.1016/s0022-3565(25)10189-4
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Abstract

The modulation of the release of substance P (SP) from sensory primary afferents by activation of kappa opioid receptors is not only equivocal, but also contradictory. Thus, in the present study, we have determined the effect of nanomolar concentrations of the highly selective kappa opioid receptor agonist trans-(+)-3,4-dichloro-N-methyl-N-[2-91- (pyrrolidinyl)cyclohexyl]benzacetamide methane sulphonate (U50488H), as well as micromolar concentrations of moderately mu-selective agonist morphine, on K(+)-evoked SP release from rat trigeminal nucleus caudalis slices. U50488H (10-30 nM) and morphine (10-30 microM) increased K(+)-evoked SP release without stimulating basal SP release. Both U50488H and morphine concentration-response curves were biphasic because the highest and the lowest concentrations of U50488H (100 nM) and morphine (3 microM) tested, respectively, inhibited SP release. Enhancement of K(+)-evoked SP release induced by 30 nM U50488H and 30 microM morphine was blocked by the opioid receptor antagonists naloxone (30 nM; nontype selective) and norbinaltorphimine (3 nM; kappa selective), but not by N,N diallyl Tyr-Aib-Aib-Phe-Leu (0.3 microM; delta selective), naloxonazine (1 nM; mu 1 selective) or beta-funaltrexamine (20 nM; mu selective). These findings indicate that activation of at least one population of kappa opioid receptors increases the release of SP from trigeminal nucleus caudalis. Excitatory presynaptic kappa opioid receptors on SP-containing primary afferents may be involved in the hyperalgesia of inflammatory processes, the "anti-analgesic" effect of dynorphin and the paradoxical "analgesia" produced by low doses of naloxone.

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Crossref · 10.1016/s0022-3565(25)10189-4

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  • This potentially indicates the involvement of other (subtypes of) (opioid) receptors.

    “Surprisingly, however, the level of mechanical antinociception produced by orphine was higher in the presence of naloxone in the current experimental setup, potentially indicating the involvement of other (subtypes of) (opioid) receptors (Bianchi and Panerai, 1993; Hamann et al., 2008, 2004; Suarez-Roca and Maixner, 1993).”

    From Elucidating the harm potential of brorphine analogues as new synthetic opioids: Synthesis, in vitro, and in vivo characterization (2024) · cites this paper as Suarez-Roca and Maixner, 1993

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Metadata

Authors
Suarez-Roca, H., & Maixner, W.
Affiliations
University of North Carolina at Chapel Hill (US)
Venue
The Journal of Pharmacology and Experimental Therapeutics
Publisher
Elsevier BV
Published
1993-02
Volume
264
Issue
2
Pages
648-653
ISSN
0022-3565 (ISSN-L)
DOI
10.1016/s0022-3565(25)10189-4
OpenAlex
W2259184966
Cited by
62
References
0
Citations by year
2024: 1 · 2020: 1 · 2019: 1 · 2016: 1 · 2012: 1
FWCI
2.55
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed
Funders
  • National Institute of Dental and Craniofacial Research (DE-08013, R29DE008013)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018968, HD-18968)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords
kappa opioid receptor, substance P release, U50,488H, morphine, trigeminal nucleus caudalis, primary afferents, naloxone, nor-binaltorphimine, dynorphin, inflammatory hyperalgesia
MeSH terms
Analgesics, Animals, Dynorphins, Male, Morphine, Naloxone, Potassium, Pyrrolidines, Substance P, Trigeminal Nuclei, Rats, Sprague-Dawley, Receptors, Opioid, kappa, 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer, Rats, In Vitro Techniques

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