Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Prostaglandin E2 (PGE2) 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 PGE2 production by ASM might be an important action of beta-adrenoceptor agonists in asthma, the regulation of PGE2 production by adenosine 3',5'-cyclic monophosphate (cAMP) was assessed using dibutyryl cAMP (DBcAMP), forskolin, and albuterol. DBcAMP increased PGE2 production over a 24-h time course. Forskolin and albuterol both increased PGE2 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 PGE2 production. Incubation of forskolin-treated cells with Rp-cAMP, a cAMP antagonist, inhibited the PGE2 response evoked by forskolin by 80%. Ro-20-1724, a selective inhibitor of type IV phosphodiesterase, stimulated PGE2 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 PGE2 production (P < 0.05). These studies suggest that cAMP may play an important regulatory role in stimulating PGE2 production by ASM. This may be a novel beneficial action of beta-adrenoceptor agonists in asthma.

Original publication

DOI

10.1152/jappl.1995.78.2.623

Type

Journal article

Journal

J Appl Physiol (1985)

Publication Date

02/1995

Volume

78

Pages

623 - 628

Keywords

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone, Albuterol, Animals, Bradykinin, Bucladesine, Cattle, Cell Count, Colforsin, Culture Media, Cyclic AMP, Cycloheximide, Dinoprostone, In Vitro Techniques, Muscle, Smooth, Phosphodiesterase Inhibitors, Trachea