Blockade of morphine analgesia by an antisense oligodeoxynucleotide against the mu receptor.
The recent cloning of mu, delta and kappa 1 opioid receptors has provide opportunities in the study of their pharmacology. Using an antisense strategy developed against delta and kappa 1 opioid receptors, we designed an antisense oligodeoxynucleotide directed against the 5'-untranslated region of MOR-1 clone, 51-70 bp upstream from the initiating ATG. Microinjection of this antisense oligodeoxynucleotide directly into the periaqueductal gray on Days 1, 3 and 5 completely blocked the analgesic actions of morphine administered into the periaqueductal gray on Day 6 (p < 0.001), 24 hr after the last antisense treatment. Rats treated with vehicle or with a mismatch oligodeoxynucleotide in which two pairs of bases from the antisense sequence had been switched were not significantly affected. These findings confirm the pharmacological relevance of the MOR-1 clone and its involvement in morphine's actions.
Rossi
G
G
Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Pan
Y X
YX
Cheng
J
J
Pasternak
G W
GW
D000698:Analgesia; D000818:Animals; D001483:Base Sequence; D008297:Male; D008845:Microinjections; D008969:Molecular Sequence Data; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000235:genetics*
D016376:Oligonucleotides, Antisense; D017450:Receptors, Opioid, mu; D009020:Morphine