Cigarette Smoking‐Associated Alterations in Serotonin/Adrenalin Signaling Pathways of Platelets

Abstract

BackgroundCigarette smoking plays a major role in cardiovascular diseases. The acute effects of cigarette smoking produce central nervous system–mediated activation of the sympathetic nervous system. The overactive sympathetic nervous system stimulates the secretion of serotonin (5‐HT) and catecholamine into blood at supraphysiological levels. The correlation between these pathological conditions induced by smoking and the increased risk of thrombosis has not been thoroughly investigated. The goal of our study was to explore cigarette smoking–associated changes in platelet biology mediated by elevated 5‐HT and catecholamine levels in blood plasma.Methods and ResultsUsing blood samples collected from healthy nonsmokers and smokers (15 minutes after smoking), we determined that cigarette smoking increased the plasma 5‐HT/catecholamine concentration by several fold and the percent aggregation of platelets 2‐fold. Liquid chromatography–tandem mass spectrometry analysis of proteins eluted from platelet plasma membranes of smokers and nonsmokers demonstrated that GTPase‐activating proteins and proteins participating in the actin cytoskeletal network were differentially and significantly elevated in smokers' platelet membranes compared with those of nonsmokers. Interestingly, Matrix‐assisted laser desorption/ionization–mass spectrometry analyses of the glycans eluted from platelet plasma membranes of the smokers demonstrated that the level and structures of glycans are different from the nonsmokers' platelet surface glycans. Pharmacological blockade of 5‐HT or catecholamine receptors counteracted the 5‐HT/catecholamine‐mediated aggregation and altered the level and composition of glycan on platelet surfaces.ConclusionsBased on our findings, we propose that smoking‐associated 5‐HT/catecholamine signaling accelerates the trafficking dynamics of platelets, and this remodels the surface proteins and glycans and predisposes platelets to hyperactive levels. Smokers' platelets also had correspondingly higher resting concentrations of intracellular calcium and transglutaminase activity. These findings suggest a link among smoking, platelet 5‐HT, catecholamine signaling, and their downstream effectors—including phospholipase C and inositol‐1,4,5‐triphosphate pathways—resulting in an increased tonic level of platelet activation in smokers.

<p>The association between <em>HTR1B</em> gene rs13212041 polymorphism and onset of alcohol abuse</p>

“…Although previous studies found decreased platelet 5-HT concentration in alcohol-dependent subjects,69–71 only one small study reported higher platelet 5-HT uptake in subjects with early than with late-onset of alcohol dependence, suggesting differences in platelet 5-HTT function 72. However, in this study as well as these in many other studies, somatic and psychiatric comorbidities and tobacco smoking have been neglected as confounding factors, in spite of reports suggesting their effects on platelet 5-HT 49,73. We observed no significant influence of somatic and psychiatric comorbidities, including depression, but smoking significantly affected platelet 5-HT levels in alcohol-dependent patients in our present and previous study 74.…”

Serotonin induced hepatic steatosis is associated with modulation of autophagy and notch signaling pathway

“…An opposite correlation of plasma serotonin levels was found in men and women which are in love and not in love [ 37 ], and elevated serotonin levels were observed in older women [ 38 ]. Peripheral serotonin levels are also correlated with various human disease conditions, for example, increased levels of serotonin in blood plasma were observed in cigarette smokers [ 39 ], patients with coronary artery disease [ 40 ] and heart failure patients [ 41 ], whereas decreased free and total serum tryptophan (a serotonin precursor) in serum and serotonin levels in whole blood were found in people after acute ethanol consumption [ 42 , 43 ]. Also, a reduction in platelet level serotonin was observed in Alzheimer’s patients [ 44 ].…”

Correlations among pain, depressive symptoms, constipation, and serotonin levels in smokers and non smokers

“…A 4.7-fold increase in plasma serotonin levels at 15 minutes after cigarette smoking was observed in smokers when compared with non smokers. 6 Plasma serotonin levels were not different between smokers and non smokers. 23 Further studies are needed to examine the correlations between serotonin levels and the duration, onset, and average daily number of cigarettes.…”

“…5 Cigarette smoking resulted in a 4.7-fold increase in plasma serotonin at 4 hours after smoking. 6 Serum serotonin was negatively correlated with depression (r = −.209, P = .001) in 320 participants. 7 Whole blood 5-hydroxytryptamine levels were positively correlated with lower gastrointestinal symptoms, such as pain around or below the belly button, resistance to bowel movements, and large bowel movements that encumbered the toilet (P = .048) in 89 children with autism spectrum disorder.…”