Evidence for various tryptamines and related compounds acting as substrates of the platelet 5-hydroxytryptamine transporter

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 1992-02, Vol.345 (2), p.129-136
• Main Authors: WÖLFEL, R, GRAEFE, K.-H
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - metabolism; Blood Proteins - metabolism; Carrier Proteins - blood; Cell physiology; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Membrane and intracellular transports; Molecular and cellular biology; Phenethylamines - metabolism; Phenethylamines - pharmacology; Rabbits; Receptors, Serotonin - drug effects; Receptors, Serotonin - metabolism; Serotonin - metabolism; Serotonin Plasma Membrane Transport Proteins; Tryptamines - metabolism; Tryptamines - pharmacology
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/BF00165727

The aim of the present study was to answer the question whether amines other than 5-hydroxytryptamine (5-HT) and tryptamine act as substrates of the platelet 5-HT transporter. To this end, a large number of tryptamines, 5-HT receptor agonists and phenethylamines (which had IC50 values for 3H-5-HT uptake inhibition of 145-24,500 nmol l-1) was examined in rabbit platelets in order to determine their ability to induce an outward transport of 3H-5-HT. Platelets (the MAO of which was blocked) from reserpine-pretreated animals were loaded with 3H-5-HT and then exposed for 5 min to various concentrations (ranging from 0.25 to 40 times the IC50) of each compound. The concentration-effect curves for the drug-induced increase in 3H-5-HT efflux served to determine values of Emax (maximum increase in efflux expressed in % of the 3H-5-HT content of cells) and EC50 (drug concentration producing Emax/2). For the 24 compounds studied here (which included the 5-HT uptake inhibitors imipramine, citalopram, fluoxetine and cocaine) a linear correlation between EC50 and IC50 (r = 0.975) and a mean ratio of EC50/IC50 of 2.4 was found. Most of the compounds +ADe.g., (+/-)8-hydroxy-2-(N,N-dipropylamino)tetralin, S(+)alpha-methyl-5-HT, 5-carboxamidotryptamine and 5-methoxytryptamine+BD gave rise to Emax values (15.8-32.5%) that exceeded that brought about by imipramine (6.6%), indicating that they act as substrates of the 5-HT transporter; the 3H-5-HT outward transport observed in response to these substances was abolished in the presence of imipramine.