+ Most Popular
Cunninghamia lanceolata plantations in China
Mammalian lairs in paleo ecological studies and palynology
Studies on technological possibilities in utilization of anhydrous milk fat for production of recombined butter-like products
Should right-sided fibroelastomas be operated upon?
Large esophageal lipoma
Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions
Poissons characoides nouveaux ou non signales de l'Ilha do Bananal, Bresil
Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices
Administration of fluid by subcutaneous infusion: revival of a forgotten method
Tundra mosquito control - an impossible dream?
Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population
Geochemical pattern analysis; method of describing the Southeastern limestone regional aquifer system
Incidence of low birth weights in a hospital of Mexico City
Graded management intensity of grassland systems for enhancing floristic diversity
Microbiology and biochemistry of cheese and fermented milk
The ember tetra: a new pygmy characid tetra from the Rio das Mortes, Brazil, Hyphessobrycon amandae sp. n. (Pisces, Characoidei)
Risk factors of contrast-induced nephropathy in patients after coronary artery intervention
Renovation of onsite domestic wastewater in a poorly drained soil
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Systolic blood pressure in a population of infants in the first year of life: the Brompton study
Haematological studies in rats fed with metanil yellow
Studies on pasteurellosis. I. A new species of Pasteurella encountered in chronic fowl cholera
Dormancy breaking and germination of Acacia salicina Lindl. seeds
therapy of lupus nephritis. a two-year prospective study

Role of carboxyl terminus of mu-and delta-opioid receptor in agonist-induced down-regulation

Role of carboxyl terminus of mu-and delta-opioid receptor in agonist-induced down-regulation

Brain Research. Molecular Brain Research 54(1): 24-34

ISSN/ISBN: 0169-328X

PMID: 9526035

Chronic exposure of mu-and delta-opioid receptors to their agonists leads to different rates in receptor down-regulation. In order to analyze the role of the carboxyl terminus of mu-and delta-opioid receptors in the difference in the rate of down-regulation, two chimeras of these receptors were generated by swapping the carboxyl termini; MORTAGDT and DORTAGMT. These chimeras were tagged at the N-terminus with hemagglutinin (HA) epitope (YPYDVPDYA), which can be recognized by the monoclonal antibody 12CA5, and then stably expressed in Neuro 2A (N2A) cells. The swapping of the carboxyl termini did not alter the ligand selectivity of these receptor chimeras. However, they did exhibit a reduction in agonist potency to inhibit forskolin-stimulated adenylyl cyclase activity for all agonists tested except etorphine which had a potency comparable to that of wild type receptors. Treatment of the N2A cells expressing MORTAGDT with 50 nM etorphine produced a faster rate of receptor down-regulation when compared to the wild type mu-opioid receptor. Immunofluorescence microscopy of the MORTAGDT chimera using a monoclonal antibody against HA confirmed internalization of the receptors after treatment with etorphine for 1 and 6h. There was a reduction in the HA-immunoreactivity at the cell surface of the MORTAGDT chimera concurrent with more noticeable HA-immunoreactivity inside the cell compared to the wild type receptor. On the other hand, the rate of down-regulation of DORTAGMT receptors was seen to be the same as the wild type delta-opioid receptor after etorphine treatment. Immunofluorescence studies showed more reduction in cell surface staining of the DORTAGMT chimera compared to the wild type receptor. These data suggest the involvement of the carboxyl terminus in agonist-induced down-regulation and internalization of the nu-opioid receptor. However, different mechanisms that are unrelated to the carboxyl terminus may operate in the down-regulation of delta-opioid receptor.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 047283405

Download citation: RISBibTeXText

Related references

Role of carboxyl terminus of μ- and δ-opioid receptor in agonist -induced down-regulation. Molecular Brain Research 54(1): 24-34, 1998

Carboxyl terminus of delta opioid receptor is required for agonist-dependent receptor phosphorylation. Biochemical and Biophysical Research Communications 238(1): 71-76, 1997

The carboxyl terminus of mouse delta-opioid receptor is not required for agonist-dependent activation. Biochemical and Biophysical Research Communications 232(2): 513-516, 1997

Sequestration of the delta opioid receptor. Role of the C terminus in agonist-mediated internalization. Journal of Biological Chemistry 271(46): 29279-29285, 1996

Role for the C-terminus in agonist-induced mu opioid receptor phosphorylation and desensitization. Biochemistry 39(18): 5492-5499, 2000

Role for the C-Terminus in Agonist-Induced Opioid Receptor Phosphorylation and Desensitization. Biochemistry 39(18): 5492-5499, 2000

Comparison of agonist-induced internalization of the human EP2 and EP4 prostaglandin receptors: role of the carboxyl terminus in EP4 receptor sequestration. Molecular Pharmacology 58(6): 1279-1286, 2000

P2X receptor chimeras highlight roles of the amino terminus to partial agonist efficacy, the carboxyl terminus to recovery from desensitization, and independent regulation of channel transitions. Journal of Biological Chemistry 288(29): 21412-21421, 2013

Inhibition of agonist-induced down-regulation of the delta-opioid receptor with a proteasome inhibitor attenuates opioid tolerance in human embryonic kidney 293 cells. Journal of Pharmacology and Experimental Therapeutics 320(3): 1186-1194, 2007

Role of protein kinase C (PKC) in agonist-induced mu-opioid receptor down-regulation: I. PKC translocation to the membrane of SH-SY5Y neuroblastoma cells is induced by mu-opioid agonists. Journal of Neurochemistry 72(2): 585-593, 1999

Differential effects of micro-opioid, delta-opioid and kappa-opioid receptor agonists on dopamine receptor agonist-induced climbing behavior in mice. Behavioural Pharmacology 17(8): 691-701, 2006

Combination of a delta opioid receptor agonist but not a mu opioid receptor agonist with the D1-selective dopamine receptor agonist SKF 38393 markedly potentiates different behaviors in mice. European Journal of Pharmacology 213(1): 25-30, 1992

Acute agonist-mediated desensitization of the human a1a-adrenergic receptor is primarily independent of carboxyl terminus regulation. Implications for regulation of a1aAR splice variants. The Journal of Biological Chemistry 277(11): 70-9, 2002

Contribution of the carboxyl terminus of the VPAC1 receptor to agonist-induced receptor phosphorylation, internalization, and recycling. Journal of Biological Chemistry 280(30): 28034-28043, 2005

Truncation of the receptor carboxyl terminus impairs agonist-induced desensitization of the type-1A angiotensin II receptor. Hypertension 28(3): 530, 1996