Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022:271:3-21.
doi: 10.1007/164_2021_433.

Fundamentals of the Dynorphins/Kappa Opioid Receptor System: From Distribution to Signaling and Function

Affiliations

Fundamentals of the Dynorphins/Kappa Opioid Receptor System: From Distribution to Signaling and Function

Catherine Cahill et al. Handb Exp Pharmacol. 2022.

Abstract

This chapter provides a general introduction to the dynorphins (DYNs)/kappa opioid receptor (KOR) system, including DYN peptides, neuroanatomy of the DYNs/KOR system, cellular signaling, and in vivo behavioral effects of KOR activation and inhibition. It is intended to serve as a primer for the book and to provide a basic background for the chapters in the book.

Keywords: In vivo pharmacology; KOR/dynorphins; Neuroanatomy; Review; Signaling.

PubMed Disclaimer

Conflict of interest statement

Conflict of interests: The authors declare no conflict of interests.

Figures

Figure 1.
Figure 1.. Summary of post-translational PDYN products, changes in chronic pain and effects on nociception, and expression patterns.
A. Dynorphin peptides are up-regulated in chronic neuropathic and inflammatory pain models (marked in red). Spinal (intrathecal) administration of DYN peptides that produce acute antinociception include Dyn A (1-8), Dyn A (1-17), Dyn B (1-13). Spinal administration of DYN peptides, Dyn A (1-17), Dyn B (1-13), Dyn A (2-17), Dyn A (2-13), produces pain-like (allodynia and hyperalgesia) responses via activation of NMDA or bradykinin receptors. [Reviewed in (Podvin et al. 2016)]. Dyn A (2-17 or 2-13) have no activity at KORs.
Figure 2.
Figure 2.
Dynorphin peptide expression in the rodent brain. L: low, M: moderate, H: high expression. Abbreviations. ARC: arcuate nucleus, hypothalamus, AMY: amygdala, BLA: basolateral nucleus, amygdala, BNST: bed nucleus of the stria terminalis, C: cerebellum, CC: corpus collosum, CeA: central nucleus, amygdala, CI: claustrum, CL: centrolateral thalamus, CM: centromedial thalamus, COA: cortical nucleus, amygdala, CPU: caudate putamen, DMH: dorsomedial hypothalamus, DMR: dorsal and medial raphe, DR: dorsal raphe, DTN: dorsal tegmental nucleus, EN: endopiriform cortex, GP: globus pallidus, HPC: hippocampus, IC: inferior colliculus, IP: interpeduncular nucleus, LC: locus coeruleus, LD: laterodorsal thalamus, LH: lateral hypothalamus, LRN: lateral reticular nucleus, ME: median eminence, MeA: median nucleus, amygdala, NAc: nucleus accumbens, NST: nucleus tractus solitarius, NL: neuronal lobe, pituitary, NRGC: nucleus reticularis gigantocellularis, OB: olfactory bulb, OCX: occipital cortex, PAG: periaqueductal gray, PBN: parabrachial nucleus, PCX: parietal cortex, PFC: prefrontal cortex, PIR: piriform cortex, PNR: pontine reticular, POA: preoptic area, PV: paraventricular thalamus, PVN: paraventricular hypothalamus, RE: reuniens thalamus, RM: raphe magnus, S: septum, SC: superior colliculus, SN: substantia nigra, STN: spinal trigeminal nucleus , Sub: subiculum, TCX: temporal cortex, Th: thalamus, TU: olfactory tubercule, VMH: ventromedial hypothalamus, VP: ventral pallidum, VR: ventral raphe, VTA: ventral tegmental area, Zi: zona incerta. [Adapted from Le Merrer et al. (2009)].
Figure 3.
Figure 3.
Expression of the KOR in rat brain. L: low, M: moderate, H: high expression. Abbreviations. ARC: arcuate nucleus, hypothalamus, AMY: amygdala, BLA: basolateral nucleus, amygdala, BNST: bed nucleus of the stria terminalis, C: cerebellum, CC: corpus collosum, CeA: central nucleus, amygdala, CI: claustrum, CL: centrolateral thalamus, CM: centromedial thalamus, COA: cortical nucleus, amygdala, CPU: caudate putamen, DMH: dorsomedial hypothalamus, DMR: dorsal and medial raphe, DR: dorsal raphe, DTN: dorsal tegmental nucleus, EN: endopiriform cortex, GP: globus pallidus, HPC: hippocampus, IC: inferior colliculus, IP: interpeduncular nucleus, LC: locus coeruleus, LD: laterodorsal thalamus, LH: lateral hypothalamus, LRN: lateral reticular nucleus, ME: median eminence, MeA: median nucleus, amygdala, NAc: nucleus accumbens, NST: nucleus tractus solitarius, NL: neuronal lobe, pituitary, NRGC: nucleus reticularis gigantocellularis, OB: olfactory bulb, OCX: occipital cortex, PAG: periaqueductal gray, PBN: parabrachial nucleus, PCX: parietal cortex, PFC: prefrontal cortex, PIR: piriform cortex, PNR: pontine reticular, POA: preoptic area, PV: paraventricular thalamus, PVN: paraventricular hypothalamus, RE: reuniens thalamus, RM: raphe magnus, S: septum, SC: superior colliculus, SN: substantia nigra, STN: spinal trigeminal nucleus , Sub: subiculum, TCX: temporal cortex, Th: thalamus, TU: olfactory tubercule, VMH: ventromedial hypothalamus, VP: ventral pallidum, VR: ventral raphe, VTA: ventral tegmental area, Zi: zona incerta. [Adapted from Le Merrer et al. (2009)].

References

    1. Al-Hasani R, Bruchas MR (2011) Molecular mechanisms of opioid receptor-dependent signaling and behavior Anesthesiology 115:1363–1381 - PMC - PubMed
    1. Ansonoff MA, Zhang J, Czyzyk T, Rothman RB, Stewart J, Xu H, Zjwiony J, Siebert DJ, Yang F, Roth BL, Pintar JE (2006) Antinociceptive and hypothermic effects of Salvinorin A are abolished in a novel strain of kappa-opioid receptor-1 knockout mice J Pharmacol Exp Ther 318:641–648 - PubMed
    1. Appleyard SM, Patterson TA, Jin WZ, Chavkin C (1997) Agonist-induced phosphorylation of the kappa-opioid receptor J Neurochem 69:2405–2412 - PubMed
    1. Arvidsson U, Riedl M, Chakrabarti S, Vulchanova L, Lee JH, Nakano AH, Lin X, Loh HH, Law P-Y, Wessendorf MW, Elde R (1995) The kappa-opioid receptor is primarily postsynaptic: combined immunohistochemical localization of the receptor and endogenous opioids Proc Natl Acad Sci U S A 92:5062–5066 - PMC - PubMed
    1. Beckett AH, Casy AF (1954) Stereochemistry of certain analgesics Nature 173:1231–1232 doi: 10.1038/1731231a0 - DOI - PubMed

LinkOut - more resources