Research Topics
| John TraynorSummaryAffiliation: University of Michigan Country: USA Publications
Research Grants
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Detail Information
Publications
Differential binding properties of oripavines at cloned mu- and delta-opioid receptorsK O Lee
Department of Pharmacology, University of Michigan, Ann Arbor 48109 0632, USA
Eur J Pharmacol 378:323-30. 1999..The ability of oripavine agonists to bind with high affinity to the low agonist affinity state of the nu-opioid receptor may explain the high potencies of these compounds in vivo...
Modulation of μ-Opioid Receptor Signaling by RGS19 in SH-SY5Y CellsQin Wang
Department of Pharmacology, 1301 MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109 5632
Mol Pharmacol 83:512-20. 2013....- μ-Opioid receptors and regulators of G protein signaling (RGS) proteins: from a symposium on new concepts in mu-opioid pharmacologyJohn Traynor
Department of Pharmacology and Substance Abuse Research Center, University of Michigan, Ann Arbor, MI 48109 5632, United States
Drug Alcohol Depend 121:173-80. 2012.... - Relationship between rate and extent of G protein activation: comparison between full and partial opioid agonistsJohn R Traynor
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0632, USA
J Pharmacol Exp Ther 300:157-61. 2002..The results are consistent with the idea that the active state(s) of the receptor induced by full or partial agonists is the same, but the number of activated receptors determines the rate of G protein activation... - Ring-constrained orvinols as analogs of buprenorphine: differences in opioid activity related to configuration of C(20) hydroxyl groupJ R Traynor
Department of Chemistry, Loughborough University, UK
J Pharmacol Exp Ther 291:1093-9. 1999..The results show that the configuration of the hydroxyl group is not important in binding affinity at mu-, delta-, or kappa-receptors but does influence kappa-potency and kappa-efficacy, particularly in vivo... - Regulators of G protein signaling & drugs of abuseJohn R Traynor
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Mol Interv 5:30-41. 2005..Finally, we consider if RGS proteins represent viable targets for drug abuse medications... 
Regulator of G protein-signaling proteins and addictive drugsJohn Traynor
Department of Pharmacology and Substance Abuse Research Center, University of Michigan, Ann Arbor, Michigan 48109 5632, USA
Ann N Y Acad Sci 1187:341-52. 2010....- Gi/o-coupled receptors compete for signaling to adenylyl cyclase in SH-SY5Y cells and reduce opioid-mediated cAMP overshootErica S Levitt
Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109 5632, USA
Mol Pharmacol 79:461-71. 2011..These results indicate that multiple receptors could be tethered into complexes with cognate signaling proteins and that access to shared AC by multiple receptor types may provide a means to prevent opioid withdrawal... - Orphanin FQ inhibits capsaicin-induced thermal nociception in monkeys by activation of peripheral ORL1 receptorsM C H Ko
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA
Br J Pharmacol 135:943-50. 2002..7. These results provide the first functional evidence that activation of peripheral ORL1 receptors produces thermal antinociception in primates and this action is independent of antinociception produced at classical opioid receptors... - Studies of micro-, kappa-, and delta-opioid receptor density and G protein activation in the cortex and thalamus of monkeysM C H Ko
Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, Ann Arbor, MI 48109 0632, USA
J Pharmacol Exp Ther 306:179-86. 2003..In particular, the relative densities of opioid receptor binding sites in the two brain areas reflect their functional roles in the pharmacological actions of opioids in the central nervous system of primates... - kappa-Opioid receptor effects of butorphanol in rhesus monkeysJ A Vivian
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA
J Pharmacol Exp Ther 290:259-65. 1999.... - Stimulation of guanosine-5'-o-(3-[35S]thio)triphosphate binding in digitonin-permeabilized C6 rat glioma cells: evidence for an organized association of mu-opioid receptors and G proteinA Alt
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0632, USA
J Pharmacol Exp Ther 298:116-21. 2001..A model that assumes an organized association of G proteins with receptors better describes the activation of G proteins by opioid mu-receptors... - The steroid 17alpha-acetoxy-6-dimethylaminomethyl-21-fluoro-3-ethoxy-pregna-3, 5-dien-20-one (SC17599) is a selective mu-opioid agonist: implications for the mu-opioid pharmacophoreI J McFadyen
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA
Mol Pharmacol 58:669-76. 2000.... - Mu and Delta opioid receptors activate the same G proteins in human neuroblastoma SH-SY5Y cellsA Alt
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-0632, USA
Br J Pharmacol 135:217-25. 2002..5. The findings support the hypothesis that mu- and delta-opioid receptors share a common G protein pool, possibly through a close organization of the two receptors and G protein at the plasma membrane... - Neutral antagonist activity of naltrexone and 6beta-naltrexol in naïve and opioid-dependent C6 cells expressing a mu-opioid receptorM F Divin
Department of Pharmacology, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI 48109 5632, USA
Br J Pharmacol 156:1044-53. 2009..This hypothesis depends on an accurate characterization of neutral and inverse agonist properties of opioid antagonists... - Roles of residues 3 and 4 in cyclic tetrapeptide ligand recognition by the kappa-opioid receptorM J Przydzial
Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
J Pept Res 65:333-42. 2005..The magnitude of this energy penalty depends on the nature of the fourth residue of the peptide (d-Pen or d-Cys) and correlates well with the observed kappa-receptor binding affinity... - The [35S]GTPgammaS binding assay: approaches and applications in pharmacologyC Harrison
Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, West Medical Center Drive, Ann Arbor, MI 48109-0632, USA
Life Sci 74:489-508. 2003.... - Antinociceptive and other behavioral effects of the steroid SC17599 are mediated by the mu-opioid receptorH Houshyar
Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA
Eur J Pharmacol 395:121-8. 2000..The steroid SC17599 is structurally a very unusually selective mu-opioid agonist that produces behavioral effects, which are similar, but not identical, to those of morphine... - Design of high affinity cyclic pentapeptide ligands for kappa-opioid receptorsM J Przydzial
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA
J Pept Res 66:255-62. 2005..Nonetheless, the high affinity KOR peptides in this series represent excellent leads for the development of structurally related, selective KOR ligands designed to exploit structurally specific features of KOR, MOR, and DOR... - Endogenous regulators of G protein signaling differentially modulate full and partial mu-opioid agonists at adenylyl cyclase as predicted by a collision coupling modelM J Clark
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA
Mol Pharmacol 73:1538-48. 2008.... - Opioids and efflux transporters. Part 2: P-glycoprotein substrate activity of 3- and 6-substituted morphine analogsChristopher W Cunningham
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, MD 21201, USA
J Med Chem 51:2316-20. 2008..Additionally, 7 demonstrated morphine-like antinociceptive potency in mice, indicating this compound as an ideal lead to further evaluate the role of P-gp in opioid analgesic tolerance development... - Differential behavioral tolerance to the delta-opioid agonist SNC80 ([(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenzamide) in Sprague-Dawley ratsEmily M Jutkiewicz
1301 MSRB III, Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109 0632, USA
J Pharmacol Exp Ther 315:414-22. 2005..Overall, the lack of observable tolerance to the antidepressant-like effects of SNC80 indicates that this class of compounds has potential as a novel antidepressant therapy... - Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in ratsEmily M Jutkiewicz
Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, Ann Arbor, MI 48109 0632, USA
Psychopharmacology (Berl) 182:588-96. 2005..Therefore, determining how to separate the convulsive and antidepressant-like characteristics of these compounds is essential for their potential clinical use... - Comparison of the opioid receptor antagonist properties of naltrexone and 6 beta-naltrexol in morphine-naïve and morphine-dependent miceMary F Divin
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109 5632, USA
Eur J Pharmacol 583:48-55. 2008.... - Characterization of opioid-binding sites in zebrafish brainVeronica Gonzalez-Nunez
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Salamanca, Spain
J Pharmacol Exp Ther 316:900-4. 2006..Hence, the study of zebrafish opioid activity may contribute to an understanding of endogenous opioid systems in higher vertebrates... - Differential in vivo potencies of naltrexone and 6beta-naltrexol in the monkeyM C Holden Ko
Department of Pharmacology, University of Michigan, Ann Arbor, 48109 0632, USA
J Pharmacol Exp Ther 316:772-9. 2006.... - Comparison of the in vitro efficacy of mu, delta, kappa and ORL1 receptor agonists and non-selective opioid agonists in dog brain membranesPatrick A Lester
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0632, USA
Brain Res 1073:290-6. 2006..The results show that the ability of agonists to stimulate [35S]GTPgammaS binding relates to the receptor distribution of opioid and ORL1 receptors in the dog... - Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ringDavid Rennison
University of Bristol, Cantock's Close, Bristol, BS8 1TS, United Kingdom
J Med Chem 49:6104-10. 2006..Wash-resistant binding was observed within this series and appeared to be unrelated to side-chain length... - Comparison of receptor mechanisms and efficacy requirements for delta-agonist-induced convulsive activity and antinociception in miceDaniel C Broom
Department of Pharmacology, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0632, USA
J Pharmacol Exp Ther 303:723-9. 2002.... - Behavioral effects of delta-opioid receptor agonists: potential antidepressants?Daniel C Broom
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109 0632, USA
Jpn J Pharmacol 90:1-6. 2002..These studies propose that the delta-opioid receptor may provide a new therapeutic target for treating human depression... - BU74, a complex oripavine derivative with potent kappa opioid receptor agonism and delayed opioid antagonismStephen M Husbands
Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK
Eur J Pharmacol 509:117-25. 2005..The slow onset, long-duration kappa opioid receptor agonist effects of BU74 suggests that it could be a lead compound for the discovery of a treatment for cocaine abuse... - Effects of substitution on the pyrrole N atom in derivatives of tetrahydronaltrindole, tetrahydrooxymorphindole, and a related 4,5-epoxyphenylpyrrolomorphinanSanjay K Srivastava
Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, U.K
J Med Chem 47:6645-8. 2004..The TOMI derivatives (8) were DOR agonists with significant selectivity. In vivo the DOR antagonist activity of 7d was confirmed, but the predominant agonist effect of 8d was shown to be mu opioid receptor mediated... - Endogenous RGS protein action modulates mu-opioid signaling through Galphao. Effects on adenylyl cyclase, extracellular signal-regulated kinases, and intracellular calcium pathwaysMary J Clark
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109 0632, USA
J Biol Chem 278:9418-25. 2003.... - Synthesis and biological evaluation of 14-alkoxymorphinans. 18. N-substituted 14-phenylpropyloxymorphinan-6-ones with unanticipated agonist properties: extending the scope of common structure-activity relationshipsElisabeth Greiner
Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria
J Med Chem 46:1758-63. 2003..09 nm)... - 4'-Arylpyrrolomorphinans: effect of a pyrrolo-N-benzyl substituent in enhancing delta-opioid antagonist activitySanjay K Srivastava
School of Chemistry, University of Bristol, Bristol BS8 1TS, UK
J Med Chem 45:537-40. 2002..In mice in vivo assays 5a showed good delta antagonist activity in the anti-writhing analgesic assay and also inhibited delta agonist-induced convulsant activity... - Delta-opioid agonists: differential efficacy and potency of SNC80, its 3-OH (SNC86) and 3-desoxy (SNC162) derivatives in Sprague-Dawley ratsEmily M Jutkiewicz
Department of Pharmacology 1301 MSRB 3, University of Michigan Medical School, Ann Arbor, MI 48109-0632, USA
J Pharmacol Exp Ther 309:173-81. 2004.... - Endogenous regulator of G protein signaling proteins suppress Galphao-dependent, mu-opioid agonist-mediated adenylyl cyclase supersensitizationMary J Clark
Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0632, USA
J Pharmacol Exp Ther 310:215-22. 2004..These results demonstrate a role for Galphao in adenylyl cyclase supersensitization after mu-agonist exposure and show that this action is modulated by endogenous RGS proteins... - Receptor binding kinetics and cellular responses of six N-formyl peptide agonists in human neutrophilsAnna Waller
Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48105, USA
Biochemistry 43:8204-16. 2004..However, the interconverting two-receptor state model was not sufficient to predict response potency, suggesting the presence of receptor states not discriminated by the binding data... - Nonpeptidic delta-opioid receptor agonists reduce immobility in the forced swim assay in ratsDaniel C Broom
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0632, USA
Neuropsychopharmacology 26:744-55. 2002..Thus, delta-agonists differ from typical antidepressants in the forced swim assay... - Characterization of the complex morphinan derivative BU72 as a high efficacy, long-lasting mu-opioid receptor agonistClaire L Neilan
Department of Pharmacology, University of Michigan, 1301 Medical Science Res. Bldg III, Ann Arbor, MI 48109, USA
Eur J Pharmacol 499:107-16. 2004..BU72 is too efficacious for human use but manipulation to reduce efficacy could provide a lead to the development of a treatment for opioid dependence... - Convulsant activity of a non-peptidic delta-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley ratsDaniel C Broom
Department of Pharmacology, University of Michigan Medical School, 1301 Medical Science Research Building III, Ann Arbor, MI 48109-0632, USA
Psychopharmacology (Berl) 164:42-8. 2002..Therefore the convulsant activity of (+)BW373U86 and possibly other non-peptidic delta-agonists is not required for activity in the forced swim assay... - The spinal antinociceptive effects of endomorphins in rats: behavioral and G protein functional studiesHong Xie
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109 0632, USA
Anesth Analg 106:1873-81. 2008..t.) administration of endomorphin-1 and -2 on nociception assays and G protein activation with those of [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), a highly effective peptidic mu-opioid receptor agonist... - Thienorphine: receptor binding and behavioral effects in rhesus monkeysJun Xu Li
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, Mail Code 7792, San Antonio, TX 78229 3900, USA
J Pharmacol Exp Ther 321:227-36. 2007..Thienorphine and U50,488 produced the same directly observable signs. These results show that thienorphine has long-lasting effects that seem to be mediated by low-efficacy agonism at kappa-opioid receptors, both in vitro and in vivo... - Nitrile analogs of meperidine as high affinity and selective sigma-1 receptor ligandsSusan L Mercer
Department of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, 20 Penn Street, Baltimore, MD 21201, USA
Eur J Med Chem 43:1304-8. 2008..The N-isobutyl, N-phenylpropyl, and N-benzyl analogs are worth pursuing due to their good affinity and selectivity at the sigma(1) receptor, whereas the N-benzyl analog exhibits the greatest selectivity for sigma(1)... - Mediation of adenylyl cyclase sensitization by PTX-insensitive GalphaoA, Galphai1, Galphai2 or Galphai3Mary J Clark
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan USA
J Neurochem 99:1494-504. 2006..This serum-mediated sensitization partially masked mu-opioid-mediated sensitization when expressed as percentage overshoot due to an apparent increase in AC activity... - Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinonesNick P R Nieland
School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK
J Med Chem 49:5333-8. 2006..The new series also followed the well-established SAR that 17-methyl ligands have greater efficacy at the mu opioid receptor than their 17-cyclopropylmethyl counterparts... - pKa and volume of residue one influence delta/mu opioid binding: QSAR analysis of tyrosine replacement in a nonselective deltorphin analogueDeborah L Heyl
Department of Chemistry, Eastern Michigan University, Ypsilanti, MI 48197, USA
Bioorg Med Chem 11:3761-8. 2003..The pK(a) effect is stronger on delta than on mu binding, generating an increase in delta selectivity with increasing residue-one pK(a)... - N-(trifluoromethyl)benzyl substituted N-normetazocines and N-norketobemidonesEverette L May
Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA
Bioorg Med Chem 11:31-3. 2003..In functional in vitro assays, this compound was a weak antagonists, but in apparent contradiction it was inactive in in vivo assays... - Assays for G-protein-coupled receptor signaling using RGS-insensitive Galpha subunitsMary J Clark
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0632, USA
Methods Enzymol 389:155-69. 2004..The altered signaling in cells expressing RGS-insensitive Galpha(o) subunits allows for determination of the role of endogenous RGS proteins to limit and/or direct signaling... - A spatial focusing model for G protein signals. Regulator of G protein signaling (RGS) protien-mediated kinetic scaffoldingHuailing Zhong
Department of Pharmacology, The University of Michigan, Ann Arbor, Michigan 48109-0632, USA
J Biol Chem 278:7278-84. 2003.... - Comparison of peptidic and nonpeptidic delta-opioid agonists on guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding in brain slices from Sprague-Dawley ratsEmily M Jutkiewicz
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0632, USA
J Pharmacol Exp Ther 312:1314-20. 2005..Finally, these data also revealed that [(35)S]GTPgammaS autoradiography could be used to compare efficacy differences among agonists across various brain regions in rat brain slices... - Major effect of pyrrolic N-benzylation in norbinaltorphimine, the selective kappa-opioid receptor antagonistCedric Chauvignac
Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
J Med Chem 48:1676-9. 2005.... - Endogenous regulator of g protein signaling proteins reduce {mu}-opioid receptor desensitization and down-regulation and adenylyl cyclase tolerance in C6 cellsMary J Clark
Department of Pharmacology, University of Michigan Medical School, 1301 Medical Science Research Building III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0632, USA
J Pharmacol Exp Ther 312:809-15. 2005..The results show that RGS proteins endogenously expressed in C6 cells reduce agonist-induced mu-opioid receptor desensitization, down-regulation, and sensitivity to tolerance to inhibit adenylyl cyclase activity... - 14-amino, 14-alkylamino, and 14-acylamino analogs of oxymorphindole. Differential effects on opioid receptor binding and functional profilesPeter Grundt
Department of Pharmacy and Pharmacology, University of Bath, UK
J Med Chem 46:1563-6. 2003.... - Identification of small-molecule inhibitors of RGS4 using a high-throughput flow cytometry protein interaction assayDavid L Roman
Department of Pharmacology, University of Michigan Medical School, 1150 W Medical Center Drive, 1303 MSRB III, Ann Arbor, MI 41809, USA
Mol Pharmacol 71:169-75. 2007..Thus, we demonstrate the feasibility of targeting RGS/Galpha protein-protein interactions with small molecules as a novel means to modulate GPCR-mediated signaling processes...
Research Grants
- OPIOID RECEPTOR MECHANISMSJohn Traynor; Fiscal Year: 2009..An understanding of roles for RGS proteins in the actions of mu-opioids may lead to improvements in the treatment of pain as well as treatment of opioid and stimulant abuse. ..
- OPIOID RECEPTOR MECHANISMSJohn R Traynor; Fiscal Year: 2010..An understanding of roles for RGS proteins in the actions of mu-opioids may lead to improvements in the treatment of pain as well as treatment of opioid and stimulant abuse. ..
- OPIOID RECEPTOR MECHANISMSJohn Traynor; Fiscal Year: 2007..An understanding of roles for RGS proteins in the actions of mu-opioids may lead to improvements in the treatment of pain as well as treatment of opioid and stimulant abuse. ..
- Role of Lipid Rafts in Adenylyl Cyclase SensitizationJohn Traynor; Fiscal Year: 2007....
- POSTDOCTORAL TRAINING IN THE BIOLOGY OF DRUG ABUSEJohn Traynor; Fiscal Year: 2007..They include state-of-the-art tools for mouse and rat genetics, genomics, proteomics, and informatics. Thus, our trainees will profit from a highly sophisticated, yet supportive, research and training environment. ..
- OPIOID RECEPTOR MECHANISMSJohn Traynor; Fiscal Year: 2007..An understanding of roles for RGS proteins in the actions of mu-opioids may lead to improvements in the treatment of pain as well as treatment of opioid and stimulant abuse. ..
- OPIOID RECEPTOR MECHANISMSJohn Traynor; Fiscal Year: 2004..The work will further define opioid signaling and suggest novel therapeutic targets for the treatment of pain and opiate drug abuse. ..