Agonist-induced internalization of κ-opioid receptors in noradrenergic neurons of the rat locus coeruleus.
Kappa-opioid receptors (κOR) are positioned to modulate pre- and post-synaptic responses of norepinephrine-containing neurons in the rat locus coeruleus (LC). The ability of an acute systemic injection of a long acting κOR agonist, U50,488, to induce trafficking of κOR was assessed in the LC using immunogold-silver detection in male Sprague-Dawley rats. U50,488 administration shifted immunogold-silver labeling indicative of κOR from primarily plasmalemmal sites to intracellular sites when compared to vehicle-treated subjects. This translocation from the plasma membrane to the cytoplasmic compartment was prevented by pre-treatment with the κOR antagonist, norbinaltorphimine (norBNI). To determine whether agonist stimulation could induce adaptations in the expression of the noradrenergic synthesizing enzyme, dopamine beta hydroxylase (DβH), and κOR expression, Western blot analysis was used to compare expression levels of DβH and κOR following U50,488 administration. Expression levels for DβH and κOR were significantly increased following U50,488 administration when compared to controls. These data indicate that a systemic injection of a κOR agonist stimulates internalization of κORs in noradrenergic neurons and can impact κOR and DβH expression levels in this stress-sensitive brain region.
Reyes
B A S
BA
Department of Neuroscience, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA. Beverly.Reyes@jefferson.edu
Chavkin
Charles
C
Van Bockstaele
E J
EJ
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage; D000818:Animals; D004299:Dopamine beta-Hydroxylase / Q000096:biosynthesis / Q000235:genetics; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D004745:Enkephalins / Q000096:biosynthesis / Q000235:genetics; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D009638:Norepinephrine / Q000502:physiology; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism* / Q000648:ultrastructure
D004745:Enkephalins; D011498:Protein Precursors; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C033660:preproenkephalin; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine