Evidence for various tryptamines and related compounds acting as substrates of the platelet 5-hydroxytryptamine transporter.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Wölfel
R
R
Institut für Pharmakologie und Toxikologie, Universität Würzburg, Federal Republic of Germany.
Graefe
K H
KH
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D010627:Phenethylamines / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D014363:Tryptamines / Q000378:metabolism* / Q000494:pharmacology
D001798:Blood Proteins; D002352:Carrier Proteins; D010627:Phenethylamines; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D014363:Tryptamines; D012701:Serotonin