PRODUCTION OF PGE(2) BY BOVINE CULTURED AIRWAY SMOOTH-MUSCLE CELLS - REGULATION BY CAMP

Prostaglandin E(2) (PGE(2)) is thought to be an important inhibitory modulator of inflammatory processes in the airway. Previous studies have shown that it is produced by bovine cultured airway smooth muscle (ASM) cells in large quantities, but its regulation by second messengers has not been studied in this tissue. To determine whether PGE(2) production by ASM might be an important action of beta-adrenoceptor agonists in asthma, the regulation of PGE(2) production by adenosine 3',5'-cyclic monophosphate (cAMP) was assessed using dibutyryl cAMP (DBcAMP), forskolin, and albuterol. DBcAMP increased PGE(2) production over a 24-h time course. Forskolin and albuterol both increased PGE(2) production over control cells to similar levels after 24 h. Incubation of albuterol-treated cells with propranolol significantly (70%) reduced the stimulatory effect of albuterol on PGE(2) production. Incubation of forskolin-treated cells with Rp-cAMP, a cAMP antagonist, inhibited the PGE(2) response evoked by forskolin by 80%. Ro-20-1724, a selective inhibitor of type IV phosphodiesterase, stimulated PGE(2) production (P = 0.02). Cycloheximide, a protein-synthesis inhibitor, did not inhibit the response to DBcAMP. The effects of DBcAMP were additive with the effects of bradykinin, a proinflammatory mediator known to increase PGE(2) production (P < 0.05). These studies suggest that cAMP may play an important regulatory role in stimulating PGE(2) production by ASM. This may be a novel beneficial action of beta-adrenoceptor agonists in asthma.