Opioid receptor internalization contributes to dermorphin-mediated antinociception

Tara A Macey; Susan L Ingram; Erin N Bobeck; Deborah M Hegarty; Sue A Aicher; Seksiri Arttamangkul; Michael M Morgan

doi:10.1016/j.neuroscience.2010.04.003

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Opioid receptor internalization contributes to dermorphin-mediated antinociception

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Opioid receptor internalization contributes to dermorphin-mediated antinociception

Tara A Macey, Susan L Ingram, Erin N Bobeck, Deborah M Hegarty, Sue A Aicher, Seksiri Arttamangkul and Michael M Morgan

Neuroscience, Vol.168(2), pp.543-550

06/30/2010

DOI: https://doi.org/10.1016/j.neuroscience.2010.04.003

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https://hdl.handle.net/2376/106294

PMCID: PMC3312465

PMID: 20394808

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https://doi.org/10.1016/j.neuroscience.2010.04.003View

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Abstract

endocytosis

periaqueductal gray

analgesia

opiate

pain modulation

Microinjection of opioids into the ventrolateral periaqueductal gray (vlPAG) produces antinociception in part by binding to mu-opioid receptors (MOPrs). Although both high and low efficacy agonists produce antinociception, low efficacy agonists such as morphine produce limited MOPr internalization suggesting that MOPr internalization and signaling leading to antinociception are independent. This hypothesis was tested in awake, behaving rats using DERM-A594, a fluorescently labeled dermorphin analog, and internalization blockers. Microinjection of DERM-A594 into the vlPAG produced both antinociception and internalization of DERM-A594. Administration of the irreversible opioid receptor antagonist beta-CNA prior to DERM-A594 microinjection reduced both the antinociceptive effect and the number of DERM-A594 labeled cells demonstrating that both effects are opioid receptor-mediated. Pretreatment with the internalization blockers dynamin dominant-negative inhibitory peptide (dynamin-DN) and concanavalinA (ConA) attenuated both DERM-A594 internalization and antinociception. Microinjection of dynamin-DN and ConA also decreased the antinociceptive potency of the unlabeled opioid agonist dermorphin when microinjected into the vlPAG as demonstrated by rightward shifts in the dose-response curves. In contrast, administration of dynamin-DN had no effect on the antinociceptive effect of microinjecting the GABA A antagonist bicuculline into the vlPAG. The finding that dermorphin-induced antinociception is attenuated by blocking receptor internalization indicates that key parts of opioid receptor-mediated signaling depend on internalization.

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Title: Opioid receptor internalization contributes to dermorphin-mediated antinociception
Creators: Tara A Macey - Department of Psychology, Washington State University Vancouver, Vancouver, WA
Susan L Ingram - Department of Psychology, Washington State University Vancouver, Vancouver, WA
Erin N Bobeck - Department of Psychology, Washington State University Vancouver, Vancouver, WA
Deborah M Hegarty - Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR
Sue A Aicher - Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR
Seksiri Arttamangkul - Vollum Institute, Oregon Health & Science University, Portland, OR
Michael M Morgan - Department of Psychology, Washington State University Vancouver, Vancouver, WA
Publication Details: Neuroscience, Vol.168(2), pp.543-550
Academic Unit: Psychology, Department of
Identifiers: 99900546937901842
Language: English
Resource Type: Journal article