Cited by 123Neuropeptides and Animal PhysiologyReceptor Mechanisms and SignalingNeurotransmitter Receptor Influence on Behavior

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Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action

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Kim, Kyoung-Shim, Lee, Ko-Woon, Lee, Kang-Woo, Im, Joo-Young, Yoo, Ji Yeoun, Kim, Seung-Woo, Lee, Ja-Kyeong, Nestler, Eric J., Han, Pyung-Lim·2006·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0508812103

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Abstract

Opioid drugs produce their pharmacological effects by activating inhibitory guanine nucleotide-binding regulatory protein-linked μ, δ, and κ opioid receptors. One major effector for these receptors is adenylyl cyclase, which is inhibited upon receptor activation. However, little is known about which of the ten known forms of adenylyl cyclase are involved in mediating opioid actions. Here we show that all of the major behavioral effects of morphine, including locomotor activation, analgesia, tolerance, reward, and physical dependence and withdrawal symptoms, are attenuated in mice lacking adenylyl cyclase type 5 (AC5), a form of adenylyl cyclase that is highly enriched in striatum. Furthermore, the behavioral effects of selective μ or δ opioid receptor agonists are lost in AC5 −/− mice, whereas the behavioral effects of selective κ opioid receptor agonists are unaffected. These behavioral data are consistent with the observation that the ability of a μ or δ opioid receptor agonist to suppress adenylyl cyclase activity was absent in striatum of AC5 −/− mice. Together, these results establish AC5 as an important component of μ and δ opioid receptor signal transduction mechanisms in vivo and provide further support for the importance of the cAMP pathway as a critical mediator of opioid action.

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Authors: Kim, K.-S., Lee, K.-W., Lee, K.-W., Im, J.-Y., Yoo, J. Y., Kim, S.-W., Lee, J.-K., Nestler, E. J., & Han, P.-L.
Affiliations: Ewha Womans University (KR)
Inha University (KR)
The University of Texas Southwestern Medical Center (US)
ORCID: Kim, Kyoung-Shim
Im, Joo-Young
Yoo, Ji Yeoun
Lee, Ja-Kyeong
Nestler, Eric J.
Han, Pyung-Lim
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2006-02-28
Volume: 103
Issue: 10
Pages: 3908-3913
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0508812103
OpenAlex: W2139496188
Cited by: 123
References: 51
Citations by year: 2026: 1 · 2025: 2 · 2024: 6 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 10 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 8 · 2015: 4 · 2014: 5 · 2013: 7 · 2012: 13
FWCI: 4.30
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 (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: adenylyl cyclase type 5, morphine, opioid receptors, mu-opioid receptor, delta opioid receptor, kappa opioid receptor, striatum, cAMP signaling, opioid tolerance, opioid reward, opioid use disorder, opioid withdrawal, analgesia, locomotor activation
MeSH terms: Adenylyl Cyclases, Animals, Behavior, Animal, Conditioning, Psychological, Corpus Striatum, Isoenzymes, Mice, Inbred C57BL, Morphine, Motor Activity, Pain Measurement, Receptors, Opioid, Substance Withdrawal Syndrome, Signal Transduction, Receptors, Opioid, mu, Receptors, Opioid, delta, Mice, Knockout, Mice

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Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action

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