Decreased platelet vesicular monoamine transporter density in habitual smokers.
The brain vesicular monoamine transporter (VMAT2) is part of the re-uptake mechanism which regulates monoaminergic neurotransmission. We demonstrated previously a high degree of similarity between the pharmacodynamic characteristics of platelet and brain VMAT2. Nicotine induced increase of dopamine and serotonin neurotransmission in limbic structures may alter the expression of VMAT2 in brains of smokers. In this study we measured the VMAT2 pharmacodynamic characteristics using high-affinity [3H]dihydrotetrabenazine (TBZOH) binding to platelets of smokers (n=15) compared to sex and age matched healthy nonsmokers controls (n=14). A significant decrease (17%, P=0.02) in VMAT2 density (Bmax) was observed in platelets of smokers compared to nonsmokers. There was no significant difference in the affinity of [3H]TBZOH to its platelet binding site and the VMAT2 density did not correlate with the heaviness of smoking. The decreased density of the VMAT2 in the platelets of smokers may reflect nicotine induced desensitization of VMAT2, a phenomenon that may be relevant to the addictive properties of nicotine.
Schwartz
Karin
K
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel.
Weizman
Abraham
A
Rehavi
Moshe
M
D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008875:Middle Aged; D011485:Protein Binding / Q000502:physiology; D012907:Smoking / Q000378:metabolism*; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; C493452:SLC18A2 protein, human; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine