Contrasting alterations in hepatic drug biotransformation of hexobarbital and p-chloro-N-methylaniline produced by prostaglandins.
The effect of prostaglandins (PGs) on the hepatic biotransformation of hexobarbital (Hechi) and p-chloro-N-methylaniline (PCMA) was determined in male rats. PCMA metabolism in slices was decreased by all PGs (PGA1, PGB1, PGE1, PGE2, PGF1alpha, PGF2alpha), ranging in concentration from 1 mu M to 1 mM. PGA1, at 1 mM, produced the greatest degree of inhibition, 39%. PG addition to microsomes, however, failed to alter PCMA metabolism. In contrast to PCMA biotransformation, Hechi metabolism was increased by all PGs in slices but not in liver subfractions. PGs of the E and F series were the most potent, producing a two-fold increase in Hechi metabolism at 1 mM after a 20 min preincubation. The increased effect was observed as early as 10 min and lasted for 4 hr. The relationship of PG metabolism and binding to cytochrome P-450 is presented as a possible mechanism to account for the opposite effects on Hechi and PCMA, type I and II substrates respectively, metabolism.
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D003640:Dealkylation; D006591:Hexobarbital / Q000378:metabolism*; D006900:Hydroxylation; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D000814:Aniline Compounds; D011453:Prostaglandins; C011716:4-chloro-N-methylaniline; D006591:Hexobarbital