Differential blockade of opioid analgesia by antisense oligodeoxynucleotides directed against various G protein α subunits Journal Article
| Authors: | Standifer, K. M.; Rossi, G. C.; Pasternak, G. W. |
| Article Title: | Differential blockade of opioid analgesia by antisense oligodeoxynucleotides directed against various G protein α subunits |
| Abstract: | Antisense oligodeoxynucleotides directed against various G protein α subunits differentially block the analgesic actions of μ-, δ- and κ- opioid agonists in mice. Intracerebroventricular administration of oligodeoxynucleotides targeting G(iα2), G(oα), and G(sα) block supraspinal μ-opioid analgesia, whereas G(iα2) and G(x/zα) antisense probes block spinal μ analgesia. Although supraspinal and spinal morphine- 6β-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. G(iα1) and Gx/zα antisense probes block supraspinal M6G analgesia, whereas G(iα1), G(iα3), G(oα), and G(x/zα) antisense probes block spinal M6G analgesia. Spinal δ-opioid analgesia is blocked by antisense probes to all of the G protein α subunits tested, whereas κ1-opioid analgesia is sensitive to only G(qα). The κ3 agonist naloxone benzoylhydrazone produces its analgesia through supraspinal mechanisms and is blocked by G(iα1), G(iα3), G(sα), G(qα), and G(x/zα) antisense oligodeoxynucleotides. Together, these results support the presence of seven different analgesic systems for these various opioid agonists. |
| Keywords: | controlled study; nonhuman; mouse; animals; mice; opiate; animal experiment; animal model; gtp-binding proteins; cell population; central nervous system; molecular cloning; molecular sequence data; drug mechanism; alternative rna splicing; base sequence; protein subunit; analgesics, opioid; guanine nucleotide binding protein; analgesia; oligonucleotides, antisense; receptor down regulation; antisense oligodeoxynucleotide; spinal anesthesia; sympathetic blocking; receptors, opioid; intracerebroventricular drug administration; male; priority journal; article; dna probe |
| Journal Title: | Molecular Pharmacology |
| Volume: | 50 |
| Issue: | 2 |
| ISSN: | 0026-895X |
| Publisher: | The American Society for Pharmacology and Experimental Therapeutics |
| Date Published: | 1996-08-01 |
| Start Page: | 293 |
| End Page: | 298 |
| Language: | English |
| PUBMED: | 8700136 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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