Loss of 5‐hydroxytryptamine from mammalian circulating labelled platelets
Authors: Osim E. E. , Wyllie J. H. 
Published: December 2014

1. Platelets were obtained from three species of animal: rats, rabbits and dogs. They were labelled with 111In oxine to tag individual platelets and with 14C‐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. 111In and 14C 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. 111In 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 111In 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 14C behaved like the 111In. However, in control rabbits the half‐life for 14C was 38·0 hr which is significantly longer than for 111In (P < 0·005). 14C also disappeared more slowly than the 111In in the dogs.

3. In all species treatment with 5‐HTP accelerated the disappearance of the 14C 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 14C/111In 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 14C in platelets. Under these conditions many tissues in addition to those above had a higher ratio of 14C/111In than platelets. These tissues included muscle, skin, salivary gland, kidney, heart, aorta, testis and seminal vesicle. As with platelets, the absolute counts of 14C/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 14C 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.