NICOTINE STEREOISOMERS AND COTININE STIMULATE PROSTAGLANDIN E-2 BUT INHIBIT THROMBOXANE B-2 AND LEUKOTRIENE E-4 SYNTHESIS IN WHOLE-BLOOD

The effects of (-)-nicotine (0.0005-500 mu M), (+)-nicotine (0.0005-50 mu M) and (-)-cotinine (0.0005-500 mu M) on arachidonic acid metaboli sm were investigated in Ca2+ ionophore A23187 (calcimycin)-stimulated human whole blood in vitro. (-)-Nicotine and (-)-cotinine stimulated p rostaglandin E-2 but inhibited thromboxane B-2 synthesis, as has been observed previously in A23187-stimulated polymorphonuclear leukocytes and platelet-rich plasma [Saareks, V., Riutta, A., Mucha, I., Alanko, J., Vapaatalo, H., 1993. Nicotine and cotinine modulate eicosanoid pro duction in human leukocytes and platelet rich plasma, fur. J. Pharmaco l., 248, 345-349.]. (+)-Nicotine also stimulated prostaglandin E-2 but inhibited thromboxane B-2 synthesis. High concentrations of(-)-nicoti ne and(-)-cotinine and even nanomolar concentrations of (+)-nicotine i nhibited leukotriene E-2 synthesis. These results indicate that (-)-ni cotine and (-)-cotinine stimulate cyclooxygenase but inhibit thromboxa ne synthase and 5-lipoxygenase in whole blood in vitro. (+)-Nicotine i s capable of affecting in the same direction as well. (C) 1998 Elsevie r Science B.V. All rights reserved.