Plasma serotonin levels and the platelet serotonin transporter

• Published in: Journal of neurochemistry Vol. 102; no. 1; pp. 206 - 215
• Main Authors: Brenner, B, Harney, J.T, Ahmed, B.A, Jeffus, B.C, Unal, R, Mehta, J.L, Kilic, F
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.07.2007; Blackwell Publishing Ltd; Blackwell
• Subjects: Arterial hypertension. Arterial hypotension; Biological and medical sciences; Biophysics; Biotin; Blood and lymphatic vessels; Blood Platelets - metabolism; Blood pressure; Blotting, Western; Cardiology. Vascular system; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell receptors; Cell structures and functions; Enzyme-Linked Immunosorbent Assay; Feedback - physiology; Fundamental and applied biological sciences. Psychology; Humans; Hypertension; Hypertension - blood; Hypotheses; Kinetics; Male; Medical sciences; Middle Aged; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); Neurotransmitters; Plasma; plasma serotonin level; platelet serotonin uptake; serotonin; Serotonin - blood; Serotonin Plasma Membrane Transport Proteins - biosynthesis; Serotonin Plasma Membrane Transport Proteins - blood; serotonin transporter; Signal transduction; Hypertension; Serotonin; Vasoconstriction; Cardiovascular disease; platelet serotonin uptake; Uptake; Blood; Vasomotricity; Chronic; Platelet; Serotonin transporter; Plasma membrane; Neurotransmitter; Models; plasma serotonin level; Biological receptor
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2007.04542.x

Serotonin (5HT) is a platelet-stored vasoconstrictor. Altered concentrations of circulating 5HT are implicated in several pathologic conditions, including hypertension. The actions of 5HT are mediated by different types of receptors and terminated by a single 5HT transporter (SERT). Therefore, SERT is a major mechanism that regulates plasma 5HT levels to prevent vasoconstriction and thereby secure a stable blood flow. In this study, the response of platelet SERT to the plasma 5HT levels was examined within two models: (i) in subjects with chronic hypertension or normotension; (ii) on platelets isolated from normotensive subjects and pretreated with 5HT at various concentrations. The platelet 5HT uptake rates were lower during hypertension due to a decrease in Vmax with a similar Km; also, the decrease in Vmax was primarily due to a decrease in the density of SERT on the platelet membrane, with no change in whole cell expression. Additionally, while the platelet 5HT content decreased 33%, the plasma 5HT content increased 33%. Furthermore, exogenous 5HT altered the 5HT uptake rates by changing the density of SERT molecules on the plasma membrane in a biphasic manner. Therefore, we hypothesize that in a hypertensive state, the elevated plasma 5HT levels induces a loss in 5HT uptake function in platelets via a decrease in the density of SERT molecules on the plasma membrane. Through the feedback effect of this proposed mechanism, plasma 5HT controls its own concentration levels by modulating the uptake properties of platelet SERT.