THE EFFECT OF 5,6-DIHYDROXYTRYPTAMINE ON UPTAKE, STORAGE AND METABOLISM OF 5-HYDROXYTRYPTAMINE BY BLOOD PLATELETS

¹ Research Department, F. Hoffmann-La Roche & Co. Ltd., Basel, Switzerland

Incubation of isolated blood platelets of rabbits or guinea pigs with 5,6-dihydroxytryptamine (5,6-DHT) caused a decrease of the 5-hydroxytryptamine (5-HT) content in whole platelets as well as in isolated 5-HT storage organelles. Histamine and adenosine 5'-triphosphate remained unchanged. On electron microscopy, the number and size of the dense osmiophilic cores of the 5-HT storage organelles was increased. These alterations were especially striking in platelets of guinea pigs which normally contain very few osmiophilic organelles. Intraperitoneal injection of 5,6-DHT to guinea pigs caused similar electron microscopic changes as those seen in the incubation experiments. No ultrastructural damage due to 5,6-DHT was detected in platelets of rabbits and guinea pigs. Paper chromatography of lysates of isolated 5-HT storage organelles from rabbit platelets incubated with 5,6-DHT revealed the presence of substantial amounts of this compound. The uptake of ¹⁴C-5-HT by isolated platelets from normal and reserpine-treated guinea pigs was competitively inhibited by 5,6-DHT. In homogenates of rabbit platelets 5,6-DHT also competitively inhibited the oxidative deamination of ¹⁴C-tyramine. It is concluded that in blood platelets 5,6-DHT acts at three different sites, i.e., the 5-HT storage organelles, the cytoplasmic membrane and the mitochondria.