Mu and delta receptors belong to a family of receptors that are coupled to potassium channels.
Open accessAbstract
The effects of agonists at mu and delta opioid receptors were compared by measuring membrane currents under voltage clamp from neurons of the rat nucleus locus coeruleus and guinea pig submucous plexus. In each tissue, the appropriate selective agonist (Tyr-D-Ala-Gly-MePhe-Gly-ol for mu receptors in locus coeruleus or Tyr-D-Pen-Gly-Phe-D-Pen for delta receptors in submucous plexus) increased the conductance of an inwardly rectifying potassium conductance and strongly hyperpolarized the membrane. The properties of the potassium conductance affected by the two opioids could not be distinguished. Experiments with intracellular application of guanosine 5'-[gamma-thio]triphosphate indicated that a guanine nucleotide-binding regulatory protein was involved in the coupling between opioid receptor and potassium channel, but there was no evidence for activation of either cAMP-dependent protein kinase or protein kinase C. It is noted that a number of vertebrate neurotransmitter receptors are coupled to potassium channels. The potassium conductance associated with these channels has properties similar to the conductance activated by mu and delta opioids; this family includes the following receptors: acetylcholine M2, norepinephrine alpha 2, dopamine D2, 5-hydroxytryptamine 5-HT1, adenosine A1, gamma-aminobutyric acid GABAB, and somatostatin. It is suggested that this conductance is a conserved neuronal effector coupled to one of the receptor types that mediates the effects of each of several major transmitters. The mu and delta opioid receptors appear to be unusual in that both utilize this same effector mechanism.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The text we found for this paper looks like another document, so the self-check wasn’t run.
Cites
Endogenous opioid peptides: multiple agonists and receptors
Lord, J. A. H., Waterfield, A. A., Hughes, J., & Kosterlitz, H. W. (1977) · Nature · doi:10.1038/267495a0 · Cited by 2,485 · see citing works
Differentiation of Receptor Systems activated by Sympathomimetic Amines
Lands, A. M., ARNOLD, A., McAuliff, J. P., Ludueña, F. P., & Brown, T. G. (1967) · Nature · doi:10.1038/214597a0 · Cited by 2,061 · see citing works
G proteins and dual control of adenylate cyclase
Gilman, A. G. (1984) · Cell · doi:10.1016/0092-8674(84)90336-2 · Cited by 1,812 · see citing works
GTP-binding proteins couple cardiac muscarinic receptors to a K channel
Pfaffinger, P. J., Martin, J. M., Hunter, D. D., Nathanson, N. M., & Hille, B. (1985) · Nature · doi:10.1038/317536a0 · Cited by 862 · see citing works
Morphine receptors as regulators of adenylate cyclase activity.
Sharma, S. K., Nirenberg, M. W., & Klee, W. A. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.2.590 · Cited by 533 · see citing works
Breitwieser, G. E., & Szabo, G. T. (1985) · Nature · doi:10.1038/317538a0 · Cited by 526 · see citing works
Newberry, N. R., & Nicoll, R. A. (1985) · The Journal of Physiology · doi:10.1113/jphysiol.1985.sp015610 · Cited by 486 · see citing works
GABAB-receptor-activated K+ current in voltage-clamped CA3 pyramidal cells in hippocampal cultures.
Gähwiler, B. H., & Brown, D. A. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.5.1558 · Cited by 478 · see citing works
Differentiation of delta and mu opiate receptor localizations by light microscopic autoradiography.
Goodman, R. R., Snyder, S. H., Kuhar, M. J., & Young, W. S. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.10.6239 · Cited by 467 · see citing works
Mode of regulation of the ACh-sensitive K-channel by the muscarinic receptor in rabbit atrial cells
Soejima, M., & Noma, A. (1984) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00587544 · Cited by 435 · see citing works
McCormick, D. A., & Prince, D. A. (1986) · Nature · doi:10.1038/319402a0 · Cited by 398 · see citing works
COLLIER, H. O. J., & Roy, A. C. (1974) · Nature · doi:10.1038/248024a0 · Cited by 374 · see citing works
Membrane properties of rat locus coeruleus neurones
Williams, J. T., North, R. A., Shefner, S. A., Nishi, S., & Egan, T. M. (1984) · Neuroscience · doi:10.1016/0306-4522(84)90265-3 · Cited by 341 · see citing works
Self-citationThe α Subunit of the GTP Binding Protein G k Opens Atrial Potassium Channels
Codina, J., Yatani, A., Grenet, D., Brown, A. M., & Birnbaumer, L. (1987) · Science · doi:10.1126/science.2436299 · Cited by 312 · see citing works
On the potassium conductance increased by opioids in rat locus coeruleus neurones.
North, R. A., & Williams, J. T. (1985) · The Journal of Physiology · doi:10.1113/jphysiol.1985.sp015743 · Cited by 268 · see citing works
Self-citationWilliams, J., Henderson, G., & North, R. A. (1985) · Neuroscience · doi:10.1016/0306-4522(85)90166-6 · Cited by 262 · see citing works
Self-citationAdenosine-activated potassium conductance in cultured striatal neurons.
Trussell, L. O., & Jackson, M. B. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.14.4857 · Cited by 252 · see citing works
The actions of noradrenaline on neurones of the rat substantia gelatinosa in vitro.
North, R. A., & Yoshimura, M. (1984) · The Journal of Physiology · doi:10.1113/jphysiol.1984.sp015141 · Cited by 251 · see citing works
Self-citationAghajanian, G. K., & Wang, Y.-Y. (1986) · Brain Research · doi:10.1016/0006-8993(86)90382-3 · Cited by 241 · see citing works
Hartzell, H. C., Kuffler, S. W., Stickgold, R., et al. (1977) · The Journal of Physiology · doi:10.1113/jphysiol.1977.sp012027 · Cited by 233 · see citing works
Aghajanian, G. K., & Lakoski, J. M. (1984) · Brain Research · doi:10.1016/0006-8993(84)91137-5 · Cited by 232 · see citing works
Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin
Yoshimura, M., & North, R. A. (1983) · Nature · doi:10.1038/305529a0 · Cited by 231 · see citing works
Self-citationMechanism of action of acetylcholine on calcium current in single cells from frog ventricle.
Fischmeister, R., & Hartzell, H. C. (1986) · The Journal of Physiology · doi:10.1113/jphysiol.1986.sp016148 · Cited by 211 · see citing works
Central and peripheral endorphins: Basic and clinical aspects
(1983) · Regulatory Peptides · doi:10.1016/0167-0115(83)90297-5 · Cited by 192 · see citing works
North, R. A., & Surprenant, A. (1985) · The Journal of Physiology · doi:10.1113/jphysiol.1985.sp015537 · Cited by 178 · see citing works
Self-citationAutoradiographic localization of μ- and δ-opiate receptors in the forebrain of the rat
McLean, S., Rothman, R. B., & Herkenham, M. A. (1986) · Brain Research · doi:10.1016/0006-8993(86)90285-4 · Cited by 171 · see citing works
Opiate-receptor interactions on single locus coeruleus neurones.
Williams, J. T., & North, R. A. (1984) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)15048-7 · Cited by 168 · see citing works
Self-citationOpiate Receptor‐Mediated Inhibition of Adenylate Cyclase in Rat Striatal Plasma Membranes
Cooper, D. M. F., Londos, C., Gill, D. L., et al. (1982) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1982.tb05365.x · Cited by 122 · see citing works
Werz, M. A., & Macdonald, R. L. (1983) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22074-2 · Cited by 119 · see citing works
Muscarinic inhibition of sympathetic C neurones in the bullfrog.
Dodd, J., & Horn, J. P. (1983) · The Journal of Physiology · doi:10.1113/jphysiol.1983.sp014494 · Cited by 108 · see citing works
Bourgoin, S., Bars, D. L., Artaud, F., et al. (1986) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24959-x · Cited by 98 · see citing works
Mihara, S., & North, R. A. (1986) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1986.tb10207.x · Cited by 95 · see citing works
Self-citationOpioid receptors: autoradiography.
Wamsley, J. K. (1983) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06573-1 · Cited by 84 · see citing works
The action of somatostatin on neurones of the myenteric plexus of the guinea‐pig ileum.
Katayama, Y., & North, R. A. (1980) · The Journal of Physiology · doi:10.1113/jphysiol.1980.sp013287 · Cited by 64 · see citing works
Self-citationDistinct Subtypes of the Opioid Receptor with Allosteric Interactions in Brain Membranes
Demoliou-Mason, C. D., & Barnard, E. A. (1986) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1986.tb00626.x · Cited by 63 · see citing works
Mammalian beta 1- and beta 2-adrenergic receptors. Immunological and structural comparisons.
Moxham, C., George, S. T., Graziano, M. P., et al. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)66907-8 · Cited by 56 · see citing works
5-Hydroxytryptamine mediates inhibitory postsynaptic potentials in rat dorsal raphe neurons
Yoshimura, M., & Higashi, H. (1985) · Neuroscience Letters · doi:10.1016/0304-3940(85)90099-0 · Cited by 52 · see citing works
Stiles, G. L., Strasser, R. H., Caron, M. G., et al. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44511-x · Cited by 50 · see citing works
Fantozzi, R., Mullikin-Kilpatrick, D., & Blume, A. J. (1981) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)13908-4 · Cited by 42 · see citing works
Functional control of the δ-opiate receptor by the inhibitory guanine nucleotide-binding protein
Milligan, G., Simonds, W. F., Streaty, R. A., et al. (1985) · Biochemical Society Transactions · doi:10.1042/bst0131110 · Cited by 19 · see citing works
Opioid inhibition of adenylate cyclase in the striatum and vas deferens of the rat
Bhoola, K. D., & Pay, S. (1986) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1986.tb11126.x · Cited by 11 · see citing works
Opiate Receptor Subtypes Associated With the Brain Mechanisms of Feeding and Reward
Wise, R. A., Jenck, F., Gratton, A. P., & Quirion, R. (1986) · PsycEXTRA Dataset · doi:10.1037/e496832006-012 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cellular and molecular mechanisms of drug dependence
Koob, G. F., & Bloom, F. E. (1988) · Science · doi:10.1126/science.2903550 · Cited by 2,070 · see citing works
Molecular mechanisms of drug addiction
Nestler, E. J. (2004) · Neuropharmacology · doi:10.1016/j.neuropharm.2004.06.031 · Cited by 1,108 · see citing works
Burkett, J. P., & Young, L. J. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2794-x · Cited by 307 · see citing works
“All three receptor types are GI protein-coupled receptors that are inhibitory when activated (Burns et al. 1983; Tsunoo et al. 1986; North et al. 1987; for a review, see Knapp et al. 1995).”
Nestler, E. J., Terwilliger, R. Z., Walker, J. R., Sevarino, K. A., & Duman, R. S. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb04602.x · Cited by 232 · see citing works
Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal
Scavone, J. L., Sterling, R. C., & Van Bockstaele, E. J. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.04.034 · Cited by 209 · see citing works
Zachariou, V., Liu, R., LaPlant, Q., Xiao, G., Renthal, W., Chan, G. C., Storm, D. R., Aghajanian, G., & Nestler, E. J. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.11.021 · Cited by 70 · see citing works
- Authors
- North, R. A., Williams, J. T., Surprenant, A., & Christie, M. J.
- Affiliations
- Oregon Health & Science University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1987-08
- Volume
- 84
- Issue
- 15
- Pages
- 5487-5491
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC298884
- OpenAlex
- W2165498557
- Cited by
- 618
- References
- 42
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 10 · 2021: 7 · 2020: 9 · 2019: 6 · 2018: 2 · 2017: 8 · 2016: 4 · 2015: 8 · 2014: 8 · 2013: 7 · 2012: 7
- FWCI
- 13.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Health and Human Services
- National Institute on Drug Abuse (DA03160, DA03161)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 32979)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- mu-opioid receptor, delta opioid receptor, potassium channels, receptor-effector coupling, G proteins, locus coeruleus neurons, submucosal plexus, hyperpolarization, neurotransmitter receptors, G protein-coupled receptors, protein kinase A, protein kinase C
- MeSH terms
- Animals, beta-Endorphin, Electric Conductivity, Endorphins, Enkephalin, Methionine, Enkephalins, Guinea Pigs, Ion Channels, Locus Coeruleus, Membrane Potentials, Narcotics, Neurons, Potassium, Receptors, Opioid, Receptors, Opioid, mu, Receptors, Opioid, delta, GTP-Binding Proteins, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, Enkephalin, D-Penicillamine (2,5)-, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review