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Molecular Pharmacology

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Abstract

Differential blockade of opioid analgesia by antisense oligodeoxynucleotides directed against various G protein alpha subunits.

K M Standifer, G C Rossi and G W Pasternak
Molecular Pharmacology August 1996, 50 (2) 293-298;
K M Standifer
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G C Rossi
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G W Pasternak
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Abstract

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.

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Molecular Pharmacology
Vol. 50, Issue 2
1 Aug 1996
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Abstract

Differential blockade of opioid analgesia by antisense oligodeoxynucleotides directed against various G protein alpha subunits.

K M Standifer, G C Rossi and G W Pasternak
Molecular Pharmacology August 1, 1996, 50 (2) 293-298;

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Abstract

Differential blockade of opioid analgesia by antisense oligodeoxynucleotides directed against various G protein alpha subunits.

K M Standifer, G C Rossi and G W Pasternak
Molecular Pharmacology August 1, 1996, 50 (2) 293-298;
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