A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence.

A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence. Abstract Text:

Heng Xu,John S Partilla,Xiaoying Wang,John M Rutherford,Kevin Tidgewell,Thomas E Prisinzano,Laura M Bohn,Richard B Rothman,Heng Xu,John S Partilla,Xiaoying Wang,John M Rutherford,Kevin Tidgewell,Thomas E Prisinzano,Laura M Bohn,Richard B Rothman,

Previous studies established that Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO) and (2S,4aR,6aR,7R,9S,10aS,10bR)-9-(Benzoyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester (herkinorin) are fully efficacious mu-agonists. Herkinorin (HERK), unlike DAMGO, does not recruit beta-arrestin and promote mu-receptor internalization, even in cells that over express beta-arrestin. We hypothesized that chronic HERK and DAMGO treatment will differentially affect cellular markers of tolerance and dependence. CHO cells expressing the cloned human mu-receptor were treated for 20 h with 10 microM DAMGO, HERK, morphine, or medium. Both DAMGO and HERK acted as full agonists in the [(35)S]GTP-gamma-S binding assay with E(MAX) values of 230% and EC(50) values of 12.8 and 92.5 nM, respectively. In the cAMP assay, DAMGO and HERK had similar E(MAX) values of approximately 80% and EC(50) values of 3.23 and 48.7 nM, respectively. Chronic exposure to both drugs produced moderate tolerance to both drugs ( approximately 2 to 5 fold) in the [(35)S]GTP-gamma-S binding assay. In the cAMP assay, chronic DAMGO produced tolerance to both drugs ( approximately 3 to 4 fold). Chronic HERK eliminated the ability of either drug to inhibit forskolin-stimulated cAMP accumulation. Chronic DAMGO increased, and chronic HERK decreased, forskolin-stimulated cAMP accumulation. Naloxone, after chronic HERK (but not DAMGO) induced a large increase in forskolin-stimulated cAMP accumulation. Viewed collectively with published data, the current data indicate that both internalizing and noninternalizing mu-agonists produce cellular signs of tolerance and dependence.

A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence. Publishing Authors By Initials

H Xu,JS Partilla,X Wang,JM Rutherford,K Tidgewell,TE Prisinzano,LM Bohn,RB Rothman,H Xu,JS Partilla,X Wang,JM Rutherford,K Tidgewell,TE Prisinzano,LM Bohn,RB Rothman,

For similar proteins: membrane proteins: receptors, cell surface: receptors, g-protein-coupled: receptors, opioid: receptors, opioid, mu research abstracts see: proteins: membrane proteins: receptors, cell surface: receptors, g-protein-coupled: receptors, opioid: receptors, opioid, mu research

PUBMED ID PMID:

MEDLINE DATE:

A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Intr

Journal: Synapse (New York, N.Y.)

VOLUME: 61

Page Numbers: 166-75

Journal Abbreviation: Synapse

ISSN: 0887-4476

DAY: 3

MONTH: Mar

YEAR: 2007

A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8806914

A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence. Keywords Mesh Terms:

KEYWORDS: Receptors, Opioid, mu

MESH TERMS: metabolism

Chemical & Substance for Abstract: A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence. Information

Substance Name: Forskolin

Registry Number: 66428-89-5

Grant and Affiliation Information for A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence.

AFFILIATION: Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, DHHS, Baltimore, Maryland 21224, USA.

Country: United States

AGENCY: United States NIDA

GRANT: R01 DA12970

ACRONYM: DA

MEDLINETA: Synapse

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

A comparison of noninternalizing herkinorin and internalizing DAMGO mu-opioid agonists on cellular markers related to opioid tolerance and dependence Related Publications

• A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence.
• Addressing the diabetes pandemic: a comprehensive approach.
• Cell-based assays using primary endothelial cells to study multiple steps in inflammation.
• Commentary: Epidemiology still ascendant.
• Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma.
• Does "excessive" anticoagulation predispose to periprosthetic infection?
• Fungus infections of the skin.
• Genetic variants in caspase genes and susceptibility to non-Hodgkin lymphoma.
• High magnetic field water and metabolite proton T1 and T2 relaxation in rat brain in vivo.
• Hypertrichosis lanuginosa?
• Impact of weight loss on the metabolic syndrome.
• Irritable bowel syndrome and hysterectomy: a sequence symmetry analysis.
• Maternal deployment of the embryonic SKN-1-->MED-1,2 cell specification pathway in C. elegans.
• Measurements of the anaplerotic rate in the human cerebral cortex using 13C magnetic resonance spectroscopy and [1-13C] and [2-13C] glucose.
• Monoamine releasers with varying selectivity for dopamine/norepinephrine versus serotonin release as candidate "agonist" medications for cocaine dependence: studies in assays of cocaine discrimination and cocaine self-administration in rhesus monkeys.
• Not Available
• PIP3 pathway in regulatory T cells and autoimmunity.
• Pharmacokinetic variability and modern epidemiology--the example of dichlorodiphenyltrichloroethane, body mass index, and birth cohort.
• Polychlorinated biphenyl levels in peripheral blood and non-Hodgkin's lymphoma: a report from three cohorts.
• Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut.
• Primary total hip arthroplasty with an uncemented femoral component: two- to seven-year results.
• Prolonged exposure to levetiracetam reveals a presynaptic effect on neurotransmission.
• Regulation of developmental rate and germ cell proliferation in Caenorhabditis elegans by the p53 gene network.
• Relationship of thrombopoietin and interleukin-11 levels to thrombocytopenia associated with dengue disease.
• Restoration of 3,4-methylenedioxymethamphetamine-induced 5-HT depletion by the administration of L-5-hydroxytryptophan.
• Scaling of dynamic contact angles in a lattice-Boltzmann model.
• Suppressor of cytokine signaling in allergic inflammation.
• The Mayo Clinic manuscript series relative to the discussion, dissemination, and operationalization of the Food and Drug Administration guidance on patient-reported outcomes.
• The effectiveness of gain-framed messages for encouraging disease prevention behavior: is all hope lost?
• The rise and fall of epidemiology, 1950-2000 A.D. 1981.