Studies on the interrelationship between the syntheses of noradrenaline and metaraminol

Br J Pharmacol. 1970 May;39(1):167-74. doi: 10.1111/j.1476-5381.1970.tb09566.x.

Abstract

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.

MeSH terms

  • Adrenal Glands / analysis
  • Animals
  • Brain Chemistry
  • Cold Temperature
  • Dihydroxyphenylalanine / biosynthesis
  • Epinephrine / analysis
  • Esters / pharmacology
  • Male
  • Metaraminol / analysis
  • Metaraminol / biosynthesis*
  • Methyltyrosines / metabolism
  • Methyltyrosines / pharmacology
  • Myocardium / analysis
  • Norepinephrine / analysis
  • Norepinephrine / biosynthesis*
  • Rats
  • Spleen / analysis
  • Stress, Physiological
  • Synaptic Transmission
  • Temperature
  • Tyramine / analysis

Substances

  • Esters
  • Methyltyrosines
  • Dihydroxyphenylalanine
  • Metaraminol
  • Norepinephrine
  • Tyramine
  • Epinephrine