![]() |
|
|
KM Standifer, GC Rossi and GW Pasternak
Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Antisense oligodeoxynucleotides directed against various G protein alpha subunits differentially block the analgesic actions of mu-, delta- , and kappa-opioid agonists in mice. Intracerebroventricular administration of oligodeoxynucleotides targeting Gi alpha 2, G(o) alpha, and Gs alpha block supraspinal mu-opioid analgesia, whereas Gi alpha 2 and Gx/z alpha antisense probes block spinal mu analgesia. Although supraspinal and spinal morphine-6 beta-glucuronide (M6G) analgesia also is sensitive to these antisense treatments, its sensitivity profile differs from that of morphine, implying the existence of a different analgesic system. Gi alpha 1 and Gx/z alpha antisense probes block supraspinal M6G analgesia, whereas Gi alpha 1, Gi alpha 3, G(o) alpha, and Gx/z alpha antisense probes block spinal M6G analgesia. Spinal delta-opioid analgesia is blocked by antisense probes to all of the G protein alpha subunits tested, whereas kappa 1- opioid analgesia is sensitive to only Gq alpha. The kappa 3 agonist naloxone benzoylhydrazone produces its analgesia through supraspinal mechanisms and is blocked by Gi alpha 1, Gi alpha 3, Gs alpha, Gq alpha, and Gx/z alpha antisense oligodeoxynucleotides. Together, these results support the presence of seven different analgesic systems for these various opioid agonists.
This article has been cited by other articles:
![]() |
R. D. Wainford, K. Kurtz, and D. R. Kapusta Central G-alpha subunit protein-mediated control of cardiovascular function, urine output, and vasopressin secretion in conscious Sprague-Dawley rats Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R535 - R542. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Zhang, J. Tetrault, W. Wang, H. H. Loh, and P.-Y. Law Short- and Long-Term Regulation of Adenylyl Cyclase Activity by {delta}-Opioid Receptor Are Mediated by G{alpha}i2 in Neuroblastoma N2A Cells Mol. Pharmacol., June 1, 2006; 69(6): 1810 - 1819. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Ueda and M. Inoue In Vivo Signal Transduction of Nociceptive Response by Kyotorphin (Tyrosine-Arginine) through Galpha i- and Inositol Trisphosphate-Mediated Ca2+ Influx Mol. Pharmacol., January 1, 2000; 57(1): 108 - 115. [Abstract] [Full Text] |
||||
![]() |
P. Sánchez-Blázquez, M. Rodríguez-Díaz, I. DeAntonio, and J. Garzón Endomorphin-1 and Endomorphin-2 Show Differences in Their Activation of {micro} Opioid Receptor-Regulated G Proteins in Supraspinal Antinociception in Mice J. Pharmacol. Exp. Ther., October 1, 1999; 291(1): 12 - 18. [Abstract] [Full Text] |
||||
![]() |
R. M. Quock, T. H. Burkey, E. Varga, Y. Hosohata, K. Hosohata, S. M. Cowell, C. A. Slate, F. J. Ehlert, W. R. Roeske, and H. I. Yamamura The delta -Opioid Receptor: Molecular Pharmacology, Signal Transduction, and the Determination of Drug Efficacy Pharmacol. Rev., September 1, 1999; 51(3): 503 - 532. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. A. Hirshman and C. W. Emala Actin reorganization in airway smooth muscle cells involves Gq and Gi-2 activation of Rho Am J Physiol Lung Cell Mol Physiol, September 1, 1999; 277(3): L653 - L661. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Leventhal, R. M. Silva, G. C. Rossi, G. W. Pasternak, and R. J. Bodnar Morphine-6beta -Glucuronide-Induced Hyperphagia: Characterization of Opioid Action By Selective Antagonists and Antisense Mapping in Rats J. Pharmacol. Exp. Ther., November 1, 1998; 287(2): 538 - 544. [Abstract] [Full Text] |
||||
![]() |
C. A. Hirshman, H. Togashi, D. Shao, and C. W. Emala Galpha i-2 is required for carbachol-induced stress fiber formation in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, November 1, 1998; 275(5): L911 - L916. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Bot, A. D. Blake, S. Li, and T. Reisine Fentanyl and its Analogs Desensitize the Cloned Mu Opioid Receptor J. Pharmacol. Exp. Ther., June 1, 1998; 285(3): 1207 - 1218. [Abstract] [Full Text] |
||||
![]() |
P. Sánchez-Blázquez and J. Garzón Delta Opioid Receptor Subtypes Activate Inositol-Signaling Pathways in the Production of Antinociception J. Pharmacol. Exp. Ther., May 1, 1998; 285(2): 820 - 827. [Abstract] [Full Text] |
||||
![]() |
M. J. Clark, P. J. Emmerson, A. Mansour, H. Akil, J. H. Woods, P. S. Portoghese, A. E. Remmers, and F. Medzihradsky Opioid Efficacy in a C6 Glioma Cell Line Stably Expressing the Delta Opioid Receptor J. Pharmacol. Exp. Ther., November 1, 1997; 283(2): 501 - 510. [Abstract] [Full Text] |
||||
![]() |
G. P. Brown, K. Yang, O. Ouerfelli, K. M. Standifer, D. Byrd, and G. W. Pasternak 3H-Morphine-6beta -Glucuronide Binding in Brain Membranes and an MOR-1-Transfected Cell Line J. Pharmacol. Exp. Ther., September 1, 1997; 282(3): 1291 - 1297. [Abstract] [Full Text] |
||||
![]() |
Y. A. Kolesnikov, Y.-X. Pan, A.-M. Babey, S. Jain, R. Wilson, and G. W. Pasternak Functionally differentiating two neuronal nitric oxide synthase isoforms through antisense mapping: Evidence for opposing NO actions on morphine analgesia and tolerance PNAS, July 22, 1997; 94(15): 8220 - 8225. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Garzón, A. García-España, and P. Sánchez-Blázquez Opioids Binding Mu and Delta Receptors Exhibit Diverse Efficacy in the Activation of Gi2 and Gx/z Transducer Proteins in Mouse Periaqueductal Gray Matter J. Pharmacol. Exp. Ther., April 1, 1997; 281(1): 549 - 557. [Abstract] [Full Text] |
||||