Evidence that endogenous 6-(ARG or LYS)-opioid peptides can interact with kappa-receptors as agonists.
Evidence is provided for the abilities of endogenous 6-(Arg or Lys)-opioid peptides to interact with kappa-receptors as agonists. Dynorphin-(1-17) and -(1-8), alpha- and beta-neo-endorphin, [Met5]-enkephalin-Arg6-Phe7 and des acetyl salmon endorphin I significantly inhibited the electrically-evoked contractions of rabbit vas deferens which had been shown to contain kappa-receptors exclusively, indicating that endogenous 6-(Arg or Lys)-opioid peptides could act on kappa-receptors as agonists. Additionally, the inhibition of contractions of rabbit vas deferens by 6-(Arg or Lys)-opioid peptides was antagonized more effectively by Mr 2266 which had a high affinity to both mu- and kappa-receptors, than naloxone which had a high affinity only to mu-receptors. This also suggested that 6-(Arg or Lys)-opioid peptides acted as kappa-receptor agonists. The rank order of the inhibitory potency of 6-(Arg or Lys)-opioid peptides against contractions of rabbit vas deferens was as follows: dynorphin-(1-17) greater than alpha-neo-endorphin greater than beta-neo-endorphin .=. dynorphin-(1-8) greater than des acetyl salmon endorphin I greater than [Met5]-enkephalin-Arg6-Phe7. Since other endogenous opioid peptides such as [Met5]- and [Leu5]-enkephalin and beta-endorphin have been shown not to act on kappa-receptors as agonist, data in the present study suggest that endogenous opioid peptides can be classified into two groups in terms of an ability to interact with kappa-receptors as an agonist.
D000818:Animals; D004399:Dynorphins; D004723:Endorphins / Q000378:metabolism* / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011498:Protein Precursors / Q000494:pharmacology; D011817:Rabbits; D011957:Receptors, Opioid / Q000378:metabolism*; D014649:Vas Deferens / Q000187:drug effects; D001615:beta-Endorphin / Q000031:analogs & derivatives*
D004723:Endorphins; D004745:Enkephalins; D011498:Protein Precursors; D011957:Receptors, Opioid; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; C025681:alpha-neoendorphin; C027511:enkephalin-Met, Arg(6)-Phe(7)-; C036449:deacetyl salmon endorphin; D004399:Dynorphins; C030719:beta-neo-endorphin