Clinical pharmacology of eicosanoids, nicotine induced changes in man.
Smoking is an important risk factor for respiratory and cardiovascular diseases. The role of numerous chemical, partly uncharacterised compounds existing in tobacco smoke is not known. (-)-Nicotine, its stereoisomer (+)-nicotine and main metabolite cotinine are biologically active compounds influencing e.g. catecholamine and eicosanoid systems. The precise mechanisms are not well known. The purpose of the present study consisting of a PhD thesis (11) and five original papers was to investigate the in vitro effects of nicotine isomers and cotinine on eicosanoid production in polymorphonuclear leukocytes, platelets and whole blood in vitro, and to clarify the effects of smoking without and with nicotine substitution on eicosanoid production in vivo and ex vivo. It was found that all the tested compounds modulated blood cell eicosanoid synthesis. Nicotine isomers and cotinine increased PGE2 but decreased TXB2, LTB4 and LTE4 synthesis in vitro. Eicosanoid synthesis in vivo and ex vivo was higher in smokers (n = 60) than in non-smoking controls (n = 20). This may contribute to the harmful cardiovascular effects of smoking. Cessation of smoking without, but not with, nicotine substitution reduced eicosanoid synthesis measured ex vivo as whole blood production or in vivo as urinary excretion of eicosanoid metabolites after 3, 7 and 14 days. Thus long-term nicotine substitution diminishes the beneficial effects of smoking cessation.
Saareks
V
V
Department of Pharmacological Sciences, University of Tampere, Finland.
Riutta
A
A
Alanko
J
J
Ylitalo
P
P
Parviainen
M
M
Mucha
I
I
Sievi
E
E
Vapaatalo
H
H
D001773:Blood Cells / Q000187:drug effects* / Q000378:metabolism; D003367:Cotinine / Q000494:pharmacology*; D015777:Eicosanoids / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D012907:Smoking; D016540:Smoking Cessation / Q000379:methods
D015777:Eicosanoids; D009538:Nicotine; D003367:Cotinine