The effect of beta-adrenergic blocking agents on experimental porphyria induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in vivo and in vitro.
The effect of DL-propranolol on 3',5'-diethoxycarbonyl-1,4-dihydrocollidine-induced experimental porphyria was studied. DL-Propranolol, a beta-adrenergic blocking agent with non-specific membrane effects, partially inhibited 3',5'-diethoxycarbonyl-1,4-dihydrocollidine-induced delta-aminolevulinate synthetase activity both in rats and in chick embryo liver cells in culture. In rats, DL-propranolol decreased urinary delta-aminolevulinate and porphobilinogen but no change occurred in the 24-h urinary excretion of total porphyrins and in the concentration of porphyrins in the liver. In cultured chick embryo liver cells treated with 3',5'-diethoxycarbonyl-1,4-dihydrocollidine, DL-propranolol decreased accumulation of porphyrins in the medium. D-Propranolol, oxprenolol and quinidine acted like DL-propranolol in chick embryo liver cells in culture treated with 3',5'-diethoxycarbonyl-1,4-dihydrocollidine. Pindolol, practolol and lidocaine had no effect. Phenobarbitone had a synergistic effect on the induction of delta-aminolevulinate synthetase by 3',5'-diethoxycarbonyl-1,4-dihydrocollidine in cultures of chick embryo liver cells. This induction was partially inhibited by propranolol. However, the increased accumulation of porphyrins in the medium caused by 3',5'-diethoxycarbonyl-1,4-dihydrocollidine was inhibited by the addition of phenobarbitone. This inhibited induction was further decreased by propranolol. Most of our results indicate that the drugs tested act mainly by their effects on membranes.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000622:Aminolevulinic Acid / Q000652:urine; D000818:Animals; D002642:Chick Embryo; D003997:Dicarbethoxydihydrocollidine; D008099:Liver / Q000378:metabolism; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D011162:Porphobilinogen / Q000652:urine; D011164:Porphyrias / Q000139:chemically induced* / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D011725:Pyridines; D051381:Rats
D000319:Adrenergic beta-Antagonists; D011166:Porphyrins; D011725:Pyridines; D003997:Dicarbethoxydihydrocollidine; D011162:Porphobilinogen; D000622:Aminolevulinic Acid; D011433:Propranolol; D000624:5-Aminolevulinate Synthetase; D010634:Phenobarbital