Sites of analgesic actions of kyotorphin and D-kyotorphin in the central nervous system of rats.
Kyotorphin(KTP) and its analog D-kyotorphin(D-KTP) which is resistant to enzyme degradation produced dose-dependent analgesic effects in the tail-pinch test when applied locally to the periaqueductal gray (PAG), nucleus reticularis paragigantocellularis(NRPG) and lumbosacral subarachnoid space(LSS) near the spinal dorsal horn in rts. ED50 values of both dipeptides at the PAG, NRPG and LSS were: 59.0, 105 and 52.6 micrograms/rat for KTP, and 6.2, 8.8 and 10.6 micrograms/rat for D-KTP, respectively. Pretreatment with naloxone(1 mg/kg s.c.) significantly inhibited the analgesic effects of KTP and D-KTP at the PAG and LSS but not at the NRPG. Simultaneous administration of bestatin (2.5 or 50 micrograms) with KTP enhanced the analgesic effect of KTP in the PAG and LSS but not in the NRPG. These findings suggest that the analgesic actions of KTP and D-KTP result from two different mechanisms, 1)enkephgalin-releasing mechanism in the PAG and spinal dorsal horn, and 2)a mechanism without involvement of enkephalin-releasing actions in the NRPG.
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D004723:Endorphins / Q000494:pharmacology*; D004745:Enkephalins / Q000378:metabolism; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012154:Reticular Formation / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects
D000700:Analgesics; D004723:Endorphins; D004745:Enkephalins; C019448:kyotorphin; D009270:Naloxone; D007930:Leucine; C012211:ubenimex