A characterization of kyotorphin (Tyr-Arg)-induced antinociception.

Intracerebroventricular administration of kyotorphin (Tyr-Arg) or Tyr-D-Arg to mice or intrathecal administration of kyotorphin to rats resulted in a dose-dependent, long-lasting, naloxone-reversible analgesia as measured by the 48 degrees C hot plate assay. The potency of kyotorphin was equal to that of Met-enkephalin although its duration of action was substantially longer. Cross-tolerance to kyotorphin could be demonstrated in animals made tolerant to morphine by chronic morphine pellet implantation. Kyotorphin was found to be inactive against column purified enkephalinase A, B and aminopeptidase and indirect evidence would suggest a lack of Met-enkephalin-releasing effect. Thus, kyotorphin represents a unique, naturally occurring peptide with in vivo narcotic-like characteristics and an unknown mechanism of action quite distinct from other opioid peptides.