The sensitivity to noxious heat in relation to brain and liver opioid glucuronidation in inbred strains of mice.
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.
Wahlström
Agneta
A
Division of Clinical Pharmacology, University Hospital, UppsalaSweden Department of Medical and Physiological Chemistry, Biomedical Center, UppsalaSweden.
Lundin
Lars-Gustav
LG
Ask
Birgitta
B
Rane
Anders
A
D000818:Animals; D001921:Brain / Q000201:enzymology*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006358:Hot Temperature; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009020:Morphine / Q000378:metabolism*; D009270:Naloxone / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D013045:Species Specificity
D009270:Naloxone; D009020:Morphine; D014453:Glucuronosyltransferase