Formation of a beta-carboline (1,2,3,4-tetrahydro-1-methyl-beta-carboline-1-carboxylic acid) following intracerebroventricular injection of tryptamine and pyruvic acid.
Tritium labelled 1-carboxy-tetrahydroharman was identified in rat brain following i.c.v.-injection of [3H]tryptamine and pyruvic acid. The animals had been treated with the MAO inhibitor pargyline (40 mg/kg) 30 min before i.c.v. injection. Under these conditions, only trace amounts of [3H]indole acetic acid could be detected in the brain. The formation of 1-CTHH was time-dependent. Five minutes following the i.c.v. injection, approximately 0.45% of the administered tryptamine was converted into 1-CTHH and 23% were still unchanged. The amount of the radioactive 1-CTHH increased slightly within 1 h (0.8%; [3H] tryptamine: 6%). Pretreatment of the rats with high doses of pargyline (75 mg/kg; 90 min before i.c.v. injection) prevented the formation of both [3H]1-CTHH and [3H]indole acetic acid (IAA) suggesting that high doses of pargyline inhibit the formation of 1-CTHH. As control for a possible non-enzymatic formation of 1-CTHH, [3H]tryptamine and various concentrations of pyruvic acid were incubated in phosphate buffer at pH 7.4. 1-CTHH was not detected under these conditions. However, the formation of 1-CTHH was observed at high pyruvic acid concentrations (final concentration = 100 mM) and low pH values (less than pH4). To support the assumption that the observed condensation of both precursors to 1-CTHH occurred intracellularly, the metabolism of tryptamine was studied. Two minutes after i.c.v. injection of [3H]tryptamine approximately 4% of the injected dose remained unchanged and 10% were metabolized to [3H]IAA. These findings suggest a rapid disappearance of [3H]tryptamine from the cerebrospinal fluid as well as a rapid penetration into the cerebral tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002243:Carbolines / Q000378:metabolism*; D003500:Cyclization; D003653:Decarboxylation; D007276:Injections, Intraventricular; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011773:Pyruvates / Q000008:administration & dosage / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D014363:Tryptamines / Q000008:administration & dosage / Q000378:metabolism*
D002243:Carbolines; D011773:Pyruvates; D014363:Tryptamines; C030820:tryptamine; C045323:harmalan; C052025:1,2,3,4-tetrahydro-1-methyl-beta-carboline-1-carboxylic acid; D019289:Pyruvic Acid