Prostaglandins: a possible mediator to inhibit hepatic drug metabolism in adjuvant arthritic rats.
In the liver of adjuvant arthritic rats perfused with a hemoglobin-free buffer solution, the rate of metabolism of a model drug, 2,6-dichloro-4-nitroanisole, was approximately half that of the control, while the bile flow rate was normal. Granulation tissue extracts and arthritic rat serum had no effect on the activity of CNA metabolism in normal rat liver preparations. In the perfused normal rat liver, the rate of CNA metabolism was inhibited by addition of prostaglandin (PG) E1, PGE2, and PGF2 alpha, respectively, in a final concentration of 0.5 microM. The inhibition by PGE1 was increased in the concentration range from 0.1 to 2.5 microM. The bile flow rate was not affected by the added PGs. However, these PGs had no direct effect on the CNA demethylating activity of the isolated hepatocytes from normal rat liver in a high concentration of 10 microM. Serotonin stimulated slightly CNA metabolism and bile production in the perfused livers by the intermittent infusion, but was without effect in the isolated hepatocytes. Epinephrine and histamine had no significant effect on CNA metabolism in both liver preparations. A similar pattern of the inhibition of CNA metabolism by PGs was reproduced in the normal rat liver perfused with the medium containing the supernatant of the hepatic nonparenchymal cells incubated in the presence of PGE1. The involvement of liver sinusoidal cells as secretory cells in depression of hepatic drug metabolism has been discussed.
Ishizuki
S
S
Kanda
N
N
Fujihira
E
E
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D000840:Anisoles / Q000378:metabolism*; D001168:Arthritis / Q000378:metabolism*; D001169:Arthritis, Experimental / Q000378:metabolism*; D015232:Dinoprostone; D004837:Epinephrine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000494:pharmacology
D000840:Anisoles; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D012701:Serotonin; C050858:2,6-dichloro-4-nitroanisole; D006632:Histamine; D000527:Alprostadil; D015232:Dinoprostone; C100006:prostaglandin F1; D004837:Epinephrine