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α‐METHYLTRYPTOPHAN: EFFECTS ON CEREBRAL MONOOXYGENASES IN VITRO AND IN VIVO
Author(s) -
Gál E. M.,
Christiansen P. A.
Publication year - 1975
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1975.tb07632.x
Subject(s) - in vivo , tryptamine , serotonin , tryptophan hydroxylase , hydroxylation , tryptophan , chemistry , 5 hydroxytryptophan , endocrinology , medicine , in vitro , tyrosine hydroxylase , pharmacology , biochemistry , enzyme , biology , serotonergic , amino acid , receptor , microbiology and biotechnology
— Following administration of x‐methyltryptophan (AMTP) (50 mg/kg) there was a time dependent decrease of serotonin and a concomitant increase of α‐methyl‐5‐hydroxy‐tryptamine (AM‐5‐HT) in most cerebral areas. AMTP is hydroxylated to α‐methyl‐5‐hydroxytryptophan (AM‐5‐HTP) by cerebral tryptophan hydroxylase in vitro and in vivo . Hydroxylation of AMTP in vitro and in vivo was markedly inhibited in p ‐chlorophenylalanine ( p ‐CP) treated rats. After administration of AMTP, the conversion in vivo of tyrosine to norepinephrine was inhibited. This inhibition was not apparent in p ‐CP pretreated animals. p ‐Chloroamphetamine ( p ‐CA) (10 mg/kg) lowered serotonin and AM‐5‐HT levels in some areas of the brain, but unlike p ‐CP, alone or in combination with AMTP it did not significantly inhibit hydroxylation of tryptophan (Trp). AMTP, as substrate of tryptophan hydroxylase, has a K m of 1.08 × 10 ‐4 M (using 6‐MPH 4 , as cofactor) and as competitive inhibitor, a K 1 of 2.09 × 10 ‐4 M with L‐Trp as substrate. AMTP becomes an uncompetitive inhibitor when its concentration is equal to or exceeds that of L‐Trp. D‐AMTP is neither a substrate nor an inhibitor of tryptophan hydroxylase. DL‐AM‐5‐HTP ( K 1 , 1.5 × 10 ‐5 M) and AM‐5‐HT ( K 1 4.0 × 10 ‐5 M) are competitive inhibitors.