The sensitivity to noxious heat in relation to brain and liver opioid glucuronidation in inbred strains of mice

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Abstract
The glucuronidation of morphine and naloxone was demonstrated in the brain and liver in 2 inbred strains of mice, C57BL/6J (B6) and DBA/2J (D2) and their F1 hybrid generation. These strains showed a significant difference in latency of withdrawal in the tail-immersion test, the B6 strain being the most sensitive. The rate of naloxone glucuronidation in the brain was 5 times higher in the B6 than in the D2 strain. In the liver the UDP-glucuronosyl transferase (UDPGT) activity was slightly higher in the D2 strain. The naloxone- and morphine-3'' glucuronide (N3G, M3G) formation rate ratio was close to 1 in both the brain and liver in all except the B6 strain, where it was 2.6 in the brain. There was a correlation between formation rate of M3G and N3G (r = 0.65 brain and r = 0.73 liver). Our results indicate a common glucuronidation pathway for morphine and naloxone.