5‐Hydroxytryptamine metabolism in sheep

Summary1 5‐Hydroxytryptamine (5‐HT) (10 mg) administered intravenously to sheep was mostly excreted in the urine as 5‐HT‐ O ‐glucuronide (705 ± 162 μg, mean from six wethers ± s . e . m .) and 5‐hydroxyindolylacetic acid (5‐HIAA) (6,850 ± 1,538 μg). Oral administration of 5‐HT (100 mg) led to the excretion of 590 ± 212 μg 5‐HT‐ O ‐glucuronide (mean from five wethers ± s . e . m .) and 7,394 ± 2,093 μg 5‐HIAA in the urine. 2 After administration of dl ‐5‐hydroxytryptophan ( dl ‐5‐HTP) (20 mg i.v. or 200 mg orally) sheep excreted about 5 mg 5‐HT in the urine together with 5‐HT‐ O ‐glucuronide and 5‐HIAA. The excretion of 5‐HT suggests that some DL‐5‐HTP perfused the liver and the lungs before being decarboxylated. 3 Twenty‐four hour specimens of control urine contained 335 ± 45 μg 5‐HT, 909 ± 90 μg 5‐HT‐ O ‐glucuronide and 3,352 ± 362 μg 5‐HIAA (seven sheep in each instance). Thus endogenous 5‐HT seemed to be conjugated with glucuronic acid to a greater extent than administered 5‐HT. 4 Although urinary 5‐HIAA was reduced after a single dose of isocarboxazid (20 mg/kg daily) the 5‐HT‐ O ‐glucuronide content of the specimens was not increased until two or three doses of the drug had been given. 5 Carbon tetrachloride (4 ml orally) reduced the urinary excretion of 5‐HT‐ O ‐glucuronide. Although the conjugation of 5‐HT with glucuronic acid was inhibited after administration of carbon tetrachloride the excretion of 5‐HT and 5‐HIAA was not increased. This observation suggests that carbon tetrachloride impaired the formation or clearance of endogenous 5‐HT in sheep.