Effect of tolmetin on responsiveness of isolated guinea pig tracheal smooth muscles

Tolmetin directly relaxed the isolated guinea pig tracheal smooth muscles, increased the muscle responsiveness to histamine or carbachol and enhanced the tracheal Schultz-Dale reaction. Prostaglandin E2 synthesized by cyclooxygenase was transformed into prostaglandin B2 (PGB2) with alkali, PGB2 and the lipoxygenase metabolite leukotriene B4 (LTB4) were measured by high-performance liquid chromatography, whereas slow-reacting substance of allergy (SRS-A) was determined by bioassay. Tolmetin showed inhibitory effects on prostaglandin E2 synthesis, with the IC50 being 30 mumol/L, but no effect on LTB4 synthesis (up to 100 mumol/L). SRS-A release was potentiated by tolmetin at 10 and 50 mumol/L. The effects of tolmetin on arachidonic acid metabolism may be responsible for its effects on tracheal smooth muscles. It is suggested that asthma attacks may be induced or enhanced by tolmetin in patients with asthma.