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 m odulator of inflammatory processes in the airway. Previous studies hav e shown that it is produced by bovine cultured airway smooth muscle (A SM) cells in large quantities, but its regulation by second messengers has not been studied in this tissue. To determine whether PGE(2) prod uction by ASM might be an important action of beta-adrenoceptor agonis ts in asthma, the regulation of PGE(2) production by adenosine 3',5'-c yclic monophosphate (cAMP) was assessed using dibutyryl cAMP (DBcAMP), forskolin, and albuterol. DBcAMP increased PGE(2) production over a 2 4-h time course. Forskolin and albuterol both increased PGE(2) product ion over control cells to similar levels after 24 h. Incubation of alb uterol-treated cells with propranolol significantly (70%) reduced the stimulatory effect of albuterol on PGE(2) production. Incubation of fo rskolin-treated cells with Rp-cAMP, a cAMP antagonist, inhibited the P GE(2) response evoked by forskolin by 80%. Ro-20-1724, a selective inh ibitor 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 e ffects 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. Th is may be a novel beneficial action of beta-adrenoceptor agonists in a sthma.