Loss of 5-hydroxytryptamine from mammalian circulating labelled platelets.

1. Platelets were obtained from three species of animal: rats, rabbits and dogs. They were labelled with (111)In oxine to tag individual platelets and with (14)C-labelled 5-hydroxytryptamine (5-HT). Doubly labelled platelets from rabbits and dogs were returned to their donors; in the case of rats the platelets were injected intravenously into other, identical rats. At time intervals from 2 to 64 hr, blood samples were drawn and platelets were collected. (111)In and (14)C were separately counted. In some experiments animals received the 5-HT precursor, 5-hydroxytryptophan (5-HTP) I.P. (for rats and rabbits) or subcutaneously (for dogs) in a dose of 20 mg/kg daily to accelerate synthesis of 5-HT.2. (111)In disappeared in approximately an exponential fashion in all experiments and the rate of disappearance was not affected by treatment with 5-HTP. The half-life for (111)In in four control rats was 18.7 hr and in five rats treated with 5-HTP was 17.8 hr. In rabbits the half-life was 20.4 hr for eight control and 21.2 hr for seven treated with 5-HTP. In the dogs the half-life was 21.0 hr for control and 27.7 hr for experiments with 5-HTP. In control rats, the (14)C behaved like the (111)In. However, in control rabbits the half-life for (14)C was 38.0 hr which is significantly longer than for (111)In (P < 0.005). (14)C also disappeared more slowly than the (111)In in the dogs.3. In all species treatment with 5-HTP accelerated the disappearance of the (14)C approximately three-fold. This was not a reserpine-like effect because the platelets contained more, not less 5-HT than usual.4. In an attempt to discover the fate of 5-HT disappearing from circulating platelets, experiments were made in which platelets from one rat were doubly labelled, and were then injected into two other rats from the identical strain; one of the recipients received daily I.P. injections of 20 mg/kg of 5-HTP. The other rat in each pair acted as a control.5. Results from twelve control rats showed that the (14)C/(111)In ratio in several tissues deviated from that found in platelets. Deviations occurred in both directions; in the spleen, liver and kidney the ratio was significantly lower than in the platelets (P < 0.01), whereas in the adrenals, thyroid, bladder and gut the ratio was significantly higher (P < 0.05 for thyroid, < 0.01 for others). In the gut, however, the ratio was significantly raised (P < 0.01) only at 5 hr.6. Administration of unlabelled 5-HTP to another twelve rats greatly reduced the (14)C in platelets. Under these conditions many tissues in addition to those above had a higher ratio of (14)C/(111)In than platelets. These tissues included muscle, skin, salivary gland, kidney, heart, aorta, testis and seminal vesicle. As with platelets, the absolute counts of (14)C/g of tissue decreased significantly after 5-HTP administration (platelets by 67%, brain by 56%, pancreas by 49%, lungs by 39%, liver by 37%, kidney by 29%, testis by 23% and seminal vesicle by 22%). On the other hand, there were significant rises of 93% in the skin and 21% in the muscle. Paper chromatography showed that 73-86% of the (14)C in tissues still behaved like 5-HT, except in the bladder and adrenals which contained unidentified material.7. It is concluded that under normal conditions platelets deposit 5-HT in specific tissues, notably gut, adrenals and thyroid. When unlabelled 5-HTP is administered, the labelled 5-HT is deposited in a variety of tissues, and especially in the skin.