Studies on the interrelationship between the syntheses of noradrenaline and metaraminol.
1. Experiments were conducted to determine the influence of the rate of noradrenaline synthesis on the conversion of alpha-methyl-m-tyrosine to metaraminol.2. Male Wistar rats, 175-200 g, were placed into four groups and treated with (1) alpha-methyl-p-tyrosine methyl ester, 250 mg/kg; (2) DL-alpha-methyl-m-tyrosine, 400 mg/kg; (3) alpha-methyl-p-tyrosine methyl ester, 250 mg/kg plus DL-alpha-methyl-m-tyrosine, 400 mg/kg; or (4) an equivalent volume of injection vehicle. All solutions were injected intraperitoneally.3. Immediately after treatment half of the rats were transferred to 4 degrees C with the remaining animals being kept at 27 degrees C.4. The rats were killed 4, 8 and 12 h after injection, the brains, hearts, spleens and adrenals removed and analysed for adrenaline, noradrenaline, metaraminol and alpha-methyl-m-tyramine.5. In virtually all cases, both during rest (27 degrees C) and sympathetic stress (4 degrees C), treatment of the rats with alpha-methyl-p-tyrosine methyl ester increased the amount of metaraminol formed from alpha-methyl-m-tyrosine. The only organ not containing increased quantities of metaraminol in the presence of alpha-methyl-p-tyrosine methyl ester was the adrenals, taken from the rats kept at 27 degrees C. Adrenals removed from the cold-exposed rats contained more metaraminol when alpha-methyl-p-tyrosine methyl ester was combined with alpha-methyl-m-tyrosine than when alpha-methyl-m-tyrosine was used alone.6. These results demonstrate that the inhibition of noradrenaline synthesis, by treatment with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine methyl ester, increased the conversion of alpha-methyl-m-tyrosine to metaraminol. It is concluded that inhibiting the formation of dopa allowed increased amounts of alpha-methyl-m-tyrosine to enter the biosynthetic pathway. These results support the false sympathetic transmitter concept advanced for metaraminol.
D000311:Adrenal Glands / Q000032:analysis; D000818:Animals; D001923:Brain Chemistry; D003080:Cold Temperature; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004837:Epinephrine / Q000032:analysis; D004952:Esters / Q000494:pharmacology; D008297:Male; D008680:Metaraminol / Q000032:analysis / Q000096:biosynthesis*; D008781:Methyltyrosines / Q000378:metabolism / Q000494:pharmacology; D009206:Myocardium / Q000032:analysis; D009638:Norepinephrine / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D013154:Spleen / Q000032:analysis; D013312:Stress, Physiological; D009435:Synaptic Transmission; D013696:Temperature; D014439:Tyramine / Q000032:analysis
D004952:Esters; D008781:Methyltyrosines; D004295:Dihydroxyphenylalanine; D008680:Metaraminol; D009638:Norepinephrine; D014439:Tyramine; D004837:Epinephrine