INVITRO ACTION OF COMBINED SALBUTAMOL AND THEOPHYLLINE ON ANAPHYLACTIC CONTRACTIONS, MEDIATOR RELEASE AND CYCLIC 3',5'-ADENOSINE-MONOPHOSPHATE IN LUNG PARENCHYMA

The mechanisms involved in the anti-asthmatic action of combined bronchodilator therapy was studied by determining the effects of combined salbutamol and theophylline on anaphylactic contractions, histamine release, prostaglandin (PG)F2α release, cyclic 3′,5′-adenosine monophosphate (c-AMP) and smooth muscle tone in guinea-pig peripheral airways in vitro. Combined, salbutamol (3 × 10-8 M) and theophylline (3 × 10-4 M) markedly inhibited anaphylactic contractions (85.8%) in lung strips. The inhibition of anaphylactic contractions was significantly greater than inhibition of histamine and PGF2α-induced contractions. Histamine release was reduced by 66.1% but PGF2α was not significantly altered. Increased c-AMP was observed with combined salbutamol (3 × 10-8 M) and theophylline (3 × 10-4 M) in the absence of antigen. The combined effect of salbutamol and theophylline was always always greater than the sum of their individual effects. The results demonstrate that in peripheral airways theophylline potentiates the action of salbutamol both directly via smooth muscle relaxation and indirectly via inhibition in mediator release. © 1979.