Nicotine stereoisomers and cotinine stimulate prostaglandin E2 but inhibit thromboxane B2 and leukotriene E4 synthesis in whole blood.
The effects of (-)-nicotine (0.0005-500 microM), (+)-nicotine (0.0005-50 microM) and (-)-cotinine (0.0005-500 microM) on arachidonic acid metabolism were investigated in Ca2+ ionophore A23187 (calcimycin)-stimulated human whole blood in vitro. (-)-Nicotine and (-)-cotinine stimulated prostaglandin E2 but inhibited thromboxane B2 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 production in human leukocytes and platelet rich plasma. Eur. J. Pharmacol., 248, 345-349.]. (+)-Nicotine also stimulated prostaglandin E2 but inhibited thromboxane B2 synthesis. High concentrations of (-)-nicotine and (-)-cotinine and even nanomolar concentrations of (+)-nicotine inhibited leukotriene E4 synthesis. These results indicate that (-)-nicotine and (-)-cotinine stimulate cyclooxygenase but inhibit thromboxane synthase and 5-lipoxygenase in whole blood in vitro. (+)-Nicotine is capable of affecting in the same direction as well.
Department of Pharmacological Sciences, University of Tampere, Finland.
V
V
Saareks
I
I
Mucha
E
E
Sievi
H
H
Vapaatalo
A
A
Riutta
D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000097:blood; D016718:Arachidonic Acid / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D003367:Cotinine / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D017999:Leukotriene E4 / Q000096:biosynthesis* / Q000097:blood; D008875:Middle Aged; D009538:Nicotine / Q000737:chemistry / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D013237:Stereoisomerism; D013929:Thromboxane B2 / Q000096:biosynthesis* / Q000097:blood
D007476:Ionophores; D016718:Arachidonic Acid; D000001:Calcimycin; D013929:Thromboxane B2; D009538:Nicotine; D017999:Leukotriene E4; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D003367:Cotinine; D015232:Dinoprostone