μ-Opioid Receptor Internalization: Opiate Drugs Have Differential Effects on a Conserved Endocytic Mechanism In Vitro and in the Mammalian Brain
μ-Opioid receptors are the pharmacological targets of endogenous opioid peptides and morphine-like alkaloid drugs. Previous studies of transfected cells and peripheral neurons indicate that opioid receptors are rapidly internalized after activation by the alkaloid agonist etorphine but not after ac...
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Veröffentlicht in: | Molecular pharmacology 1998-03, Vol.53 (3), p.377 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | μ-Opioid receptors are the pharmacological targets of endogenous opioid peptides and morphine-like alkaloid drugs. Previous
studies of transfected cells and peripheral neurons indicate that opioid receptors are rapidly internalized after activation
by the alkaloid agonist etorphine but not after activation by morphine. To determine whether opioid receptors in the central
nervous system are regulated by a similar process of agonist-selective internalization, μ-opioid receptors were examined in
rat brain neurons after treatment of animals with opioid drugs. Internalized μ receptors were observed within 30 min after
intraperitoneal injection of the alkaloid agonist etorphine, and this process was blocked by the antagonist naloxone. Colocalization
of internalized opioid receptors with transferrin receptors in confocal optical sections indicated that receptor internalization
observed in vivo is mediated by a membrane trafficking pathway similar to that observed previously in vitro using transfected human embryonic kidney 293 cells. Morphine failed to induce detectable rapid internalization of receptors,
even when administered to animals at doses far in excess of those required to induce analgesia. To quantify these agonist-selective
differences and to analyze an array of opioid ligands for their ability to trigger internalization, we used flow cytometry
on stably transfected 293 cells. These studies indicated that the different effects of individual agonists are not correlated
with their potencies for receptor activation and that a variety of clinically important agonists differ significantly in their
relative abilities to stimulate the rapid internalization of opioid receptors. |
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ISSN: | 0026-895X 1521-0111 |