5-hydroxytryptamine metabolism in sheep.

1. 5-Hydroxytryptamine (5-HT) (10 mg) administered intravenously to sheep was mostly excreted in the urine as 5-HT-O-glucuronide (705+/-162 mug, mean from six wethers+/-S.E.M.) and 5-hydroxyindolylacetic acid (5-HIAA) (6,850+/-1,538 mug). Oral administration of 5-HT (100 mg) led to the excretion of 590+/-212 mug 5-HT-O-glucuronide (mean from five wethers+/-S.E.M.) and 7,394+/-2,093 mug 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 mug 5-HT, 909+/-90 mug 5-HT-O-glucuronide and 3,352+/-362 mug 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.