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Cited by 73Neurotransmitter Receptor Influence on BehaviorReceptor Mechanisms and SignalingNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.

Specific Binding of [ 11 C]Raclopride and N -[ 3 H]Propyl-Norapomorphine to Dopamine Receptors in Living Mouse Striatum: Occupancy by Endogenous Dopamine and Guanosine Triphosphate–Free G Protein

Cumming, Paul, Wong, Dean F., Gillings, Nicholas, Hilton, John, Scheffel, Ursula, Gjedde, Albert·2002·Journal of Cerebral Blood Flow & Metabolism
DOI 10.1097/00004647-200205000-00011
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Abstract

According to the ternary complex model of G-protein linkage to receptors, agonists increase the affinity of the receptors for the G protein. The model predicts that an endogenous agonist's constant of inhibition toward an agonist radioligand is lower than that toward an antagonistic radioligand. The authors hypothesized that competition from endogenous dopamine in striatum of living mice should have a greater effect on the binding of the D 2,3 partial agonist N-[ 3 H]propylnorapomorphine than on the binding of the D 2,3 antagonist [ 11 C]raclopride. The baseline binding potential ( p B(0) ), defined as the ratio of bound-to-unbound ligand in the absence of competition from endogenous dopamine, was simultaneously measured in mouse striatum for [ 11 C]raclopride ( p B(0) = 8.5) and N-[ 3 H]propylnorapomorphine ( p′ B(0 ) = 5.3). The baseline was established by treatment with α-methyl- p-tyrosine and reserpine. Relative to these baseline values in saline-treated mice, the p B of N-[ 3 H]propylnorapomorphine decreased 52% whereas the p B of [ 11 C]raclopride decreased only 30%, indicating greater sensitivity of the former compound to inhibition by synaptic dopamine. Furthermore, amphetamine decreased the p B of N-[ 3 H]propylnorapomorphine to a greater extent (73%) than that of [ 11 C]raclopride (43%) relative to the reserpine condition. For both radioligands, the occupancy of the dopamine receptors by endogenous agonist obeyed Michaelis-Menten kinetics over a wide range of agonist concentrations established by the pharmacologic treatments. The apparent inhibition constant of endogenous dopamine depended on the dopamine occupancy and decreased to a value 1.66 times greater for N-[ 3 H]propylnorapomorphine than for [ 11 C]raclopride at its highest occupancies. The results are consistent with the hypothesis that agonist binding is more sensitive than antagonist binding to competition from endogenous dopamine. Therefore, dopamine agonist ligands may be superior to benzamide antagonist ligands for the estimation of dopamine receptor occupancy by endogenous synaptic dopamine. The analysis of the effect of dopamine occupancy on the inhibition of N-[ 3 H]propylnorapomorphine binding indicated a limited supply of G protein with a maximum ternary complex fraction of 40% of maximum agonist binding capacity.

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Crossref · 10.1097/00004647-200205000-00011

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45 of 45 references verified0 citation errors · 0 not checkable

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  • The corresponding Ki values against [123I]-DOI indicated ten-fold higher affinity at 5HT2A sites, presumably indicative of the greater competition between an agonist drug at agonist-labelled receptors, as has been established for the case of dopamine D2/3 receptors.

    “The corresponding Ki values against [123I]-DOI indicated ten-fold higher affinity at 5HT2A sites [10,14], which is presumably indicative of the greater competition between an agonist drug at agonist-labelled receptors, as has been established for the case of dopamine D2/3 receptors [46].”

    From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [46]

Citations

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Research works printed but not linked: 9

  1. Cresse I., 1979, Commun Psychopharmacol, 3, 385
  2. Gillings N., 2000, Paper presented at the 7th International Symposium on the Synthesis of Isotopes and Isotopically Labeled Compounds
  3. Gjedde A., 1990, Quantitative imaging of neuroreceptors, 51
  4. Levant B., 1997, Pharmacol Rev, 49, 221
  5. Michaelis L., 1913, Biochem Z, 49, 333
  6. Ross S.B., 1989, Naunyn Schmiedebergs Arch Pharmacol, 340, 13
  7. Ross S.B., 1989, Naunyn Schmiedebergs Arch Pharmacol, 340, 6
  8. Tarazi F.I., 1997, Psychopharmacology, 17, 186
  9. Watts V.J., 1996, Mol Pharmacol, 50, 966

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Metadata

Authors
Cumming, P., Wong, D. F., Gillings, N., Hilton, J., Scheffel, U., & Gjedde, A.
Affiliations
  • Aarhus University Hospital (DK)
  • Johns Hopkins University (US)
Corresponding author
Cumming, Paul
ORCID
Venue
Journal of Cerebral Blood Flow & Metabolism
Publisher
SAGE Publications
Published
2002-05
Volume
22
Issue
5
Pages
596-604
ISSN
  • 0271-678X (ISSN-L)
  • 1559-7016
DOI
10.1097/00004647-200205000-00011
OpenAlex
W1986885544
Cited by
71
References
45
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 2 · 2016: 3 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 1
FWCI
1.98
Type
journal article
Language
en
Open access
closed
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01da011080-05)
  • National Institute on Alcohol Abuse and Alcoholism (R01 AA 1283)
  • National Institute of Mental Health (R01 MH 4282)
  • National Institute on Drug Abuse (R01DA11080, R01 DA 094821)
  • National Institute of Neurological Disorders and Stroke (K24 NS 389279)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
dopamine D2/D3 receptors, endogenous dopamine, receptor occupancy, ternary complex model, G protein coupling, [11C]raclopride, striatum, amphetamine, Michaelis-Menten kinetics, binding potential, alpha-methyl-p-tyrosine
MeSH terms
Animals, Apomorphine, Carbon Radioisotopes, Corpus Striatum, Dopamine, Kinetics, Male, Protein Binding, Receptors, Dopamine, Tritium, GTP-Binding Proteins, Raclopride, Mice

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