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

Title
Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action
Authors
Kim K.-S.Lee K.-W.Im J.-Y.Yoo J.Y.Kim S.-W.Lee J.-K.Nestler E.J.Han P.-L.
Ewha Authors
한평림
SCOPUS Author ID
한평림scopus
Issue Date
2006
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
ISSN
0027-8424JCR Link
Citation
vol. 103, no. 10, pp. 3908 - 3913
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © 2006 by The National Academy of Sciences of the USA.
DOI
10.1073/pnas.0508812103
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일반대학원 > 뇌·인지과학과 > Journal papers
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