Shape change and uptake of 5-hydroxytryptamine in human blood platelets: action of neuropsychotropic drugs.

Psychotropic drugs acted as agonists, antagonists or mixed agonists-antagonists of the shape change mediated by the 5HT receptor in blood platelets of man incubated in a protein-poor medium. Regarding inhibition of 5HT uptake some of the drugs were equally potent in both reserpinized and normal platelets, whereas others showed lower or higher potencies in the former than in the latter. There was no correlation between the potencies of the drugs as shape change inhibitors and as uptake inhibitors. It is concluded that 1) human platelets may serve as models for the neuronal 5HT receptors of some areas of the central nervous system, 2) platelets can be used to determine the subcellular site of action of 5HT uptake inhibitors and 3) the receptors responsible of the shape change, and the site of the 5HT transport at the plasma membrane are different entities.     

Uptake of gamma-aminobutyric acid by human blood platelets: comparison with CNS uptake

Human blood platelets show a sodium and temperature dependent uptake of gamma-aminobutyric acid (GABA) and other neuroactive amino acids. The most potent inhibitors tested of platelet GABA uptake were taurine and beta-alanine, while nipecotic acid and cis-3-aminocyclohexanecarboxylic acid were relatively weak inhibitors. These results suggest GABA is transported by a beta-amino acid uptake process in human platelets. Thus, platelet GABA uptake may more closely resemble glial rather than neuronal uptake.     

Specific binding sites for 5-hydroxytryptamine on rat blood platelets.

5-Hydroxytryptamine changes the shape of rat blood platelets by combination with a cinanserin-sensitive receptor which is not associated with the active uptake of 5-hydroxytryptamine. Binding of 5-hydroxy[3H]tryptamine to platelets at 4 degrees C demonstrates the presence of three saturable sites, and the highest-affinity site is apparently this 5-hydroxytryptamine receptor.     

Sodium-dependent transport of 5-hydroxytryptamine (serotonin) by canine blood platelets

The transport of 5-hydroxytryptamine (5-HT) was shown to be strongly dependent on the presence of Na⁺ in the incubation medium whereas divalent cations were without effect. The K_m for the Na⁺ requirement was 16.8 mm. The addition of Na⁺ to Na⁺-depleted platelets restored maximum 5-HT transport within 3 min. The affinity of the 5-HT carrier for its substrate was directly proportional to the concentration of Na⁺; however, below 25 mm Na⁺ unique reversible morphological changes in platelet shape occurred as revealed by scanning electron microscopy which resulted in a drastically reduced affinity for 5-HT. K⁺, choline (Ch⁺), or Li⁺ could be used as counterbalancing cations to maintain osmolarity, and the affinity for 5-HT was also dependent on the concentrations of these ions. Ouabain as well as various ionophores at low concentrations inhibited 5-HT uptake. The inhibition was the result of the destruction of the $\text{Na}{}^{\mathrm{+}}\text{K}{}^{\mathrm{+}}$ gradient across the cytoplasmic membrane. Ionophores, however, did not cause the depletion of either intracellular ATP or 5-HT.     

Elevation of the cyclic GMP concentration in human platelets by sodium ascorbate and 5-hydroxytryptamine.

Sodium L-ascorbate (ascorbate) and sodium D-ascorbate produced a dose-related rise of guanosine 3':5'-cyclic monophosphate (cGMP) in platelets with a maximum increment averaging 25-fold at 5 mM ascorbate. The ascorbate-induced increment in cGMP reached a peak after 1 min and was maintained for 1 h in the presence of ascorbate. 5-hydroxytryptamine (5-HT) also produced a dose-related rise of cGMP in platelets with a peak effect of approximately 25-fold at 16 micrometer 5-HT. The elevation of cGMP in platelets by both ascorbate and 5-HT did not require extracellular calcium and was blocked by inhibitors of cyclo-oxygenase such as aspirin or indomethacin. A maximum ascorbate-induced rise in platelet cGMP at the time of addition of epinephrine, collage or thrombin did not augment the release of [14C]5-hydroxytryptamine ([14C]5-HT) measured over 30 min. Although ascorbate appeared to increase platelet cGMP by modulation of endoperoxide formation, its failure to aggregate platelets or to influence the release reaction indicates that the ascorbate-stimulated rise in cGMP does not have a simple relationship to thromboxane formation.     

Uptake of 5-hydroxytryptamine by blood platelets in Huntington's chorea and Alzheimer type of presenile dementia

Kinetics of 5-HT uptake by blood platelets was studied om eleven patients with Huntington's chorea and in ten patients with presenile dementia of Alzheimer type. In both groups of patients 5-HT uptake was unchanged in comparison to that of respective controls of the same age. The results do not confirm earlier reports of an increased 5-HT uptake by blood platelets in Huntington's chorea. Platelet 5-HT uptake does not seem to serve as biological test in either disease.