The effect of naloxone on enkephalin catabolism.

Naloxone strongly inhibited the breakdown of Met- and Leu-enkephalin when the substrate was incubated with brain homogenate, supernatant, or partially purified soluble aminopeptidase, but it had no effect on the mitochondrial fraction. Arylamidase was also inhibited by naloxone. The inhibitory effect of naloxone on the soluble aminopeptidase was in a linear relationship with concentration in the range of 8-500 microM. The KI for Met-enkephalin is 0.6 mM and for Leu-enkephalin is 2.0 mM. When the naloxone was administered intraperitoneally to the mice, its effects were somewhat different from its effects in vitro. It inhibited the brain catabolism of Met-enkephalin but not of Leu-enkephalin or Tyr-beta NA in vitro. In vivo, acute morphine in mice decreased the Met-enkephalin hydrolysis but increased the Leu-enkephalin hydrolysis. Chronic morphine (by morphine pellet implantation) increased the breakdown rate of enkephalin and of Tyr-beta NA. Naloxone (1 mg/kg) could not reverse the effects of morphine, although abstinence syndrome and stereotypical jumping were precipitated. Naloxone decreased the Leu-enkephalin level in the control mice but did not affect it in the addicted mice.