In recent years, evidence has been obtained that aromatic monoamines-for example, catecholamines and 5-hydroxytryptamine (5HT)-might function as neurohumoral transmitters in the central nervous system, and knowledge of their transfer, storage and metabolism is therefore important. Direct investigations of these processes, for example, in isolated synaptosomes of the brain, are, however, problematic since these elements have to be separated from their natural environment and connexions by rather crude methods (for example, density gradient centrifugation of brain homogenates). Blood platelets which contain substantial amounts of 5HT seem to be more appropriate models in spite of the fact that the function of the amine in this situation is not well understood. Thus, the platelets can be studied in relatively physiological conditions in vitro-for example, in plasma or artificial buffer systems-and they also have the capacity to metabolize, transfer and store 5HT.Some recent findings in this laboratory concerning the metabolism, transfer and storage of 5HT in blood platelets are reported here. Platelets of various species including man were isolated according to the usual procedures (Bartholini, Pletscher & Gey, 1961) and in most of the experiments incubated in buffers such as Tyrode using disodium-ethylenediaminetetraacetate to prevent platelet aggregation. Experiments with plasma as an incubation medium did not differ markedly from those with Tyrode.
METABOLISM
Physiological conditionsIn isolated blood platelets incubated for several hours in physiological media such as plasma or Tyrode buffer, the 5HT content is lowered only slightly (by 1-5%) (Fig. 1) Paasonen & Pletscher, 1959). The small amounts of 5HT which are lost from the platelets hardly appear as such in the incubation medium, but in the form of two major metabolites. They show the typical activation and fluorescent spectra of 5-hydroxyindole derivatives and have RF values characteristic of 5-hydroxyindoleacetic acid (5HIAA) and 5-hydroxytryptophol (5HT'ol) on paper and thin-layer chromatography (Fig. 2). Platelets also metabolize exogenous 5HT (Bartholini, Pletscher * Michael Cross Memorial Lecture 1967. 2 A. PLETSCHER Reserpine p-Chlorometamphetamine 100\ 50 0so 1 0 30 60 120 0 30 60 120 Min~utes Fig. 1. Effect of reserpine (2.5 jig/ml.) and p-chlorometamphetamine-HBr (100 jig/ml.) on the metabolism of 5-hydroxytryptamine (5HT) in rabbit platelets incubated in Tyrode at 370 C. The 5HT and 5-hydroxyindoleacetic acid (5HIAA) are expressed as a percentage of the 5HT content in platelets before incubation with the drugs. ----, 5HT of platelets; ...., 5HT of
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