The decarboxylation of amino acids related to tyrosine and their awakening action in reserpine‐treated mice

Abstract

Recent work on the formation of catechol amines in mammals hasshown that the amino acid L-DOPA (fl-3:4-dihydroXy-L-phenylalanine) is the immediate precursor of adrenaline, noradrenaline and dopamine (fl-3:4-dihydroxyphenylethylamine). DOPA is decarboxylated by DOPA decarboxylase, an enzyme present in many tissues, including chromaffin and nervous tissue (see Blaschko, 1959).Although the molecule of DOPA is believed to be devoid of intrinsic pharmacological activity in intact animals, it has in vivo some sympathomimetic actions which are believed to be due to the catechol amines produced by the decarboxylation of L-DOPA. Also, in mice and monkeys tranquillized by reserpine, large doses of DOPA have a remarkable awakening effect (Carlsson, Lindqvist & Magnusson, 1957; Everett & Toman, 1959), caused probably by the catechol amines which are formed from it.Much infcrmation is available on the substrate specificity of DOPA decarboxylase. This enzyme acts not only on 3:4-DOPA, presumably its natural substrate, but also on a number of other amino acids, mostly hydroxylated derivatives of phenylalanine. These observations, summarized elsewhere (Blaschko, 1950;Sourkes, 1955), have shown that the 2:5-and the 2:3-isomers of DOPA are readily decarboxylated by preparations of rat and guinea-pig tissues. L-Tyrosine is not decarboxylated, but its meta-hydroxy analogue (hereafter called metatyrosine) is a substrate of the mammalian enzyme, and it has recently been shown that in normal mice, rats, rabbits and dogs metatyrosine has excitatory actions, which are also thought to be due to the amine formed by the decarboxylation of the amino acid (Mitoma, Posner, Bogdanski & Udenfriend, 1957).In the present study we have first tested the substrate specificity of the DOPA decarboxylase in the mouse and then examined a number of amino acids related to 3:4-DOPA for their awakening action in mice tranquillized * Rockefeller Fellow.

Trace amine-associated receptor 1—Family archetype or iconoclast?

“…Although simple in concept it proved difficult in practice to unquestionably demonstrate that a similar aromatic amino acid decarboxylase (AADC) enzymatic activity was endogenous to animal tissues (Blaschko, 1942;Blaschko & Chrusciel, 1960;Lovenberg et al, 1962) and can yield both PEA Mosnaim et al, 1974) and TYR (Boulton & Quan, 1970; although other routes of synthesis certainly exist (Boulton & Quan, 1970;Sabelli et al, 1975).…”

Phosphaturic effect of dopamine in dogs. Possible role of intrarenally produced dopamine in phosphate regulation.

“…Dopa is probably an inert compound (16)(17)(18), which, when infused, increases the renal content of dopamine (5)(6)(7). In intact dogs, renal artery infusions of dopa were phosphaturic.…”

Effect of folic acid by mouth on cerebrospinal fluid homovanillic acid and 5-hydroxyindoleacetic acid concentration

“…Increased dopamine turnover after L-dopa administration may cause alerting (Blaschko and Chrusciel, 1960) but also increases CSF HVA (Curzon et al, 1970). However, HVA formation requires two enzymes (Axelrod, 1966), the intraneuronal monoamine oxidase and the extraneuronal catecholamine-O-methyl transferase.…”