Kentsin: tetrapeptide from hamster embryos produces naloxone-sensitive effects without binding to opioid receptors.
The opioid nature of kentsin (Thr-Pro-Arg-Lys) and its ability to alter pain perception and intestinal transit were examined. Kentsin (30,000 nM) did not inhibit electrically stimulated contractions of the guinea pig ileum (GPI) or mouse vas deferens (MVD), nor did it cause a rightward displacement of the inhibitory concentration-response curves of the mu-selective opioid agonist PL017 in the GPI or the delta-selective agonist DPDPE in the MVD. Kentsin (10,000 nM) did not displace [3H] naloxone from rat brain homogenates. These results indicate that kentsin lacks opioid agonist and mu and delta opioid antagonist properties and does not bind to opioid receptors. In vivo, kentsin produced dose-dependent analgesia in both the hotplate and abdominal stretch tests when administered intracerebroventricularly (ICV) and intrathecally but not intravenously. The central analgesic effect of kentsin was partially antagonized by the opioid antagonist naloxone. Kentsin inhibited intestinal transit in a dose-dependent manner after ICV administration only. The intestinal antitransit effect of kentsin was not blocked by pretreatment with naloxone. These results suggest that kentsin acts centrally to produce both opioid and non-opioid effects. Further, the opioid-mediated analgesic effects of kentsin involve mechanisms other than direct interaction with opioid receptors.
Fox
D A
DA
Ayres
E A
EA
Wire
W S
WS
Lui
G
G
Yamamura
H I
HI
Burks
T F
TF
D000818:Animals; D001921:Brain / Q000378:metabolism; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D004622:Embryo, Mammalian; D006168:Guinea Pigs; D007082:Ileum; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009270:Naloxone / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D014649:Vas Deferens
D009842:Oligopeptides; D011957:Receptors, Opioid; D009270:Naloxone; C017147:kentsin