Cigarette smoke extracts inhibit prostacyclin synthesis by the rat urinary bladder

Since prostacyclin (PGI2) is known to have a cytoprotective effect on epithelia, and since cigarette smoking is associated with an increased risk of bladder cancer, we investigated the possibility that nicotine, cotinine (the principal metabolite of nicotine) and other components of cigarette smoke inhibit PGI2 secretion by the urinary bladder. Using the rat urinary bladder as a model, we found that cigarette smoke extracts, but not nicotine or cotinine, inhibit in vitro PGI2 synthesis. 2-Naphthylamine, a known bladder carcinogen, was also a potent inhibitor of PGI2 synthesis by the rat bladder. It is possible that cigarette smoke and 2-napthylamine exert their carcinogenic effect partly through the inhibition of PGI2 synthesis, resulting in diminished urothelial cytoprotection.