Selective induction of xenobiotic metabolizing esterases/amidases of liver by methaqualone consumption.
The present investigation reports the influence of po and ip methaqualone administration on the hydrolytic metabolism of acetylsalicylic acid, procaine, p-nitrophenylacetate, acetanilid, and butyrylcholine in the liver, kidney, and brain of male rats. Oral administration of methaqualone (60 mg/kg/day) to rats for 20 days caused 41.0, 46.5, and 55.0% stimulation of acetylsalicyclic acid esterase I, acetylsalicyclic acid esterase II, and acetanilid N-deacetylase, respectively, in the liver. Under such conditions, the activities of other esterases remained unaffected. The responses of tissue esterases to ip methaqualone treatment (40 mg/kg/day for 6 days) were similar to those observed after po methaqualone administration. Since a single po dose of methaqualone failed to produce any alteration in the rate of metabolism of acetylsalicylic acid, procaine, p-nitrophenylacetate, acetanilid, and butyrylcholine within 20 hr, it may be interpreted that the stimulation of acetylsalicylic acid and acetanilid metabolism is possibly due to selective enhanced de novo synthesis of the enzymes/isozymes necessary for the hydrolysis of the two drugs. The ability of the kidney and brain to metabolize the esters/amides was not modified by po or ip methaqualone pretreatment suggesting the possibility of noninducible forms of renal and neuronal esterases/amidases.
D000581:Amidohydrolases / Q000096:biosynthesis*; D000818:Animals; D001241:Aspirin / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004950:Esterases / Q000096:biosynthesis*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008702:Methaqualone / Q000494:pharmacology*; D011343:Procaine / Q000378:metabolism; D051381:Rats
D011343:Procaine; D008702:Methaqualone; D004950:Esterases; D000581:Amidohydrolases; D001241:Aspirin