Increased Serotonin Receptor Density and Platelet GPIIb/IIIa Activation Among Smokers

Abstract

Abstract-This study sought to determine whether depressive symptoms and/or platelet serotonin receptor (5HT 2A ) density are associated with increased platelet activation (PA) found among smokers. Flow cytometric detection of PA was used to study 36 smokers and 16 nonsmokers, aged 18 to 48 years. Subjects were tested at baseline and after either smoking 2 cigarettes (smokers) or a similar resting interval (nonsmokers). Assessment of PA included both platelet secretion and fibrinogen receptor (GPIIb/IIIa) binding. Platelet 5HT 2A receptor binding and saturation were tested using [ 3 H]LSD, and depressive symptoms were measured using the Beck Depression Inventory. Platelet 5HT 2A receptor density was increased among smokers versus nonsmokers (82.7Ϯ67.7 versus 40.0Ϯ20.2 fmol/mg protein; PϽ0.005), and there was a dose-dependent relationship between receptor density and packs/d among smokers. Baseline wound-induced GPIIb/IIIa binding at 1 minute and GPIIb/IIIa binding in response to collagen stimulation in vitro was increased among smokers (PϽ0.05); there were no changes in PA among smokers after smoking, and platelet secretion was not elevated among smokers. Depressive symptoms were associated with 5HT 2A receptor density among nonsmokers (PϽ0.005), but no such relationship was evident among smokers; PA was unrelated to 5HT 2A receptor density in either group. The findings indicate that smoking is associated with increased platelet serotonin receptor density and with increased GPIIb/IIIa receptor binding, although these 2 factors are not related to each other or to depressive symptoms among smokers. Serotonergic dysfunction may be an important factor in the development of cardiovascular disease among smokers.

Serotonin receptors in platelets of bipolar and schizoaffective patients: effect of lithium treatment

“…In a recent study, Steckler et al (1993) Our results should be interpreted with caution. Smoking (Markovitz et al 1999) and progesterone or estrogen (for review, see Berendsen 2000) have been shown to cause changes in 5HT 2A receptors. We did not have adequate information on the patients' smoking history, and the stages of the menstrual cycle in female patients, and hence we cannot exclude the possibility that the increases in 5HT 2A receptors in our BP or SA patients may be related to these factors.…”

5-Hydroxytryptamine 5-HT2A receptor and 5-hydroxytryptamine transporter polymorphisms in acute myocardial infarction

“…Cigarette smoking is strongly associated with MI in our population, and smokers are likely to have an increased platelet 5-HT #A receptor density [5]. First, we analysed a limited number of patients and control subjects.…”

Platelet glycoprotein IIb polymorphism, traditional risk factors and non‐fatal myocardial infarction in young women

“…the identification of individuals particularly likely to benefit from glycoprotein IIb/IIIa inhibitor therapy). Cigarette smoking is associated with increased glycoprotein IIb/IIIa receptor activation (Markovitz et al , 1999), as well as with increased circulating levels of fibrinogen (Folsom, 1999), the ligand that binds to glycoprotein IIb/IIIa. These findings provide possible mechanisms underlying the synergism we observed between the genetic variant of platelet glycoprotein IIb and smoking in the pathogenesis of acute MI.…”