G-protein antisense oligodeoxyribonucleotides and mu-opioid supraspinal antinociception.
The present study utilized an in vivo antisense strategy to examine the functional interaction of supraspinal mu-opioid receptors with the G protein subunits Gi1 alpha, Gi2 alpha, Gi3 alpha and Gs alpha. Mice were injected intracerebroventricularly (i.c.v.) with 33-base phosphorothioate oligodeoxyribonucleotides (12.5 micrograms) or with vehicle in equal volume (sterile water, 5 microliters) and the antinociceptive responses to i.c.v. morphine [D-Ala2,NMePhe4,Gly5-ol]enkephalin (DAMGO) or sufentanil were determined 18-24 h later using the tail-flick test. Treatment with antisense to Gi2 alpha, but not the other subunits, significantly attenuated morphine-induced antinociception. The degree of attenuation for the three mu-opioid agonists was in the order morphine > DAMGO > sufentanil, the inverse of their intrinsic efficacy.
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R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776.
Martinez
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Connelly
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D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D004347:Drug Interactions; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism*; D017409:Sufentanil / Q000494:pharmacology
D000700:Analgesics; D004745:Enkephalins; D016376:Oligonucleotides, Antisense; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; D017409:Sufentanil; D019204:GTP-Binding Proteins