Internalization of mu-opioid receptors in rat spinal cord slices.
Cells immunoreactive for the mu-opioid receptor (MOR) in laminae I-II of the spinal cord were identified as small neurons with rostro-caudal dendrites. In spinal cord slices, [D-Ala2,MePhe4-Gly-ol5]enkephalin (DAMGO) or etorphine (1 microM) caused naloxone-sensitive MOR endocytosis in 100% of these neurons, whereas the selective delta- and kappa-opioid agonists [D-Pen2,5]enkephalin (DPDPE) and spiradoline mesylate (U-62,066), respectively, produced negligible internalization at 1 microM. The EC50 for DAMGO was 30 nM, similar to its potency to inhibit cAMP accumulation and to increase [gamma-35S]GTP binding. MOR internalization followed an exponential timecourse with a half-life of 1.7 min. MOR internalization in spinal cord slices was faster and occurred at lower agonist concentrations than in MOR-transfected cells, suggesting that spinal cord neurons have a more effective coupling of MORs to intracellular components mediating endocytosis.
Marvizón
J C
JC
Department of Medicine and Physiology, University of California, Los Angeles 90095, USA.
Grady
E F
EF
Waszak-McGee
J
J
Mayer
E A
EA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007700:Kinetics; D051381:Rats; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D014018:Tissue Distribution / Q000502:physiology
D004745:Enkephalins; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-