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) o n prostaglandin E(2) and leukotriene B-4 production in human polymorph onuclear leukocytes and on thromboxane B-2 formation in human platelet -rich plasma, stimulated by calcium ionophore A23187. Nicotine and cot inine dose-dependently increased prostaglandin E(2) synthesis in polym orphonuclear leukocytes from 25% (0.5 nM) up to nearly four-fold (0.5 mM). In concentrations found in the plasma of smokers, nicotine and co tinine increased prostaglandin E(2) production by 33% (50 nM) and 50% (500 nM), respectively. Nicotine and cotinine equipotentially reduced both leukotriene B-4 production in polymorphonuclear leukocytes and th romboxane B-2 production in platelet rich plasma, the inhibition incre asing from 20% (0.5 nM) to 60% (0.5 mM). The stimulation of prostaglan din E(2) and inhibition of leukotriene B-2 and thromboxane B-2 product ion by nicotine and cotinine may due to the pyridine moiety that these compounds have in common.