Nicotine and cotinine modulate eicosanoid production in human leukocytes and platelet rich plasma.
We investigated the effects of nicotine and cotinine (0.5 nM-0.5 mM) on prostaglandin E2 and leukotriene B4 production in human polymorphonuclear leukocytes and on thromboxane B2 formation in human platelet-rich plasma, stimulated by calcium ionophore A23187. Nicotine and cotinine dose-dependently increased prostaglandin E2 synthesis in polymorphonuclear leukocytes from 25% (0.5 nM) up to nearly four-fold (0.5 mM). In concentrations found in the plasma of smokers, nicotine and cotinine increased prostaglandin E2 production by 33% (50 nM) and 50% (500 nM), respectively. Nicotine and cotinine equipotentially reduced both leukotriene B4 production in polymorphonuclear leukocytes and thromboxane B2 production in platelet rich plasma, the inhibition increasing from 20% (0.5 nM) to 60% (0.5 mM). The stimulation of prostaglandin E2 and inhibition of leukotriene B4 and thromboxane B2 production by nicotine and cotinine may due to the pyridine moiety that these compounds have in common.
Saareks
V
V
Department of Biomedical Sciences, University of Tampere, Finland.
Riutta
A
A
Mucha
I
I
Alanko
J
J
Vapaatalo
H
H
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003367:Cotinine / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis* / Q000097:blood; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D011863:Radioimmunoassay; D012907:Smoking / Q000097:blood; D013929:Thromboxane B2 / Q000096:biosynthesis
D007975:Leukotriene B4; D000001:Calcimycin; D013929:Thromboxane B2; D009538:Nicotine; D003367:Cotinine; D015232:Dinoprostone