Possible regulatory role of dynorphin on morphine- and beta-endorphin-induced analgesia.
In previous studies, we observed that dynorphin- (1-13), but not dynorphin-(1-9), can significantly inhibit morphine- or beta-endorphin-induced analgesia despite not having any appreciable analgesic activity itself. Dynorphin-(1-13) showed no inhibitory effect on Sandoz FK33824-induced analgesia. In the present study, we examined the effect of dynorphin on morphine-, beta-endorphin-, D-ala2-D-leu5-enkephalin- or Sandoz FK33824-induced analgesia in both naive, morphine-tolerant and morphine-dependent mice. It was found that although dynorphin may inhibit morphine- or beta-endorphin-induced analgesia in naive animals, the peptide is not effective in inhibiting D-ala2-D-leu5-enkephalin- or Sandoz FK33824-induced analgesia. Dynorphin is also effective in blocking spontaneous withdrawal jumping in morphine-dependent animals. It is suggested that dynorphin-(1-13) may play a modulatory role in regulating analgesia due to morphine or beta-endorphin, but not that due to enkephalin. The action of peptides on morphine- or beta-endorphin-induced analgesia in the naive state is different from that of the tolerant state, suggesting that dynorphin may be involved in the development of morphine tolerance and physical dependence.
D000700:Analgesics / Q000037:antagonists & inhibitors; D000818:Animals; D004347:Drug Interactions; D004361:Drug Tolerance; D004399:Dynorphins; D004723:Endorphins / Q000494:pharmacology*; D004745:Enkephalins / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control; D001615:beta-Endorphin
D000700:Analgesics; D004723:Endorphins; D004745:Enkephalins; D001615:beta-Endorphin; D004399:Dynorphins; D009020:Morphine