Enhancement by reproterol of the ability of disodium cromoglycate to stabilize rat mastocytes

The beta2-adrenoceptor agonist reproterol and disodium cromoglycate (DSCG) are used in fixed combination for the treatment of asthma, because they act on bronchial smooth muscle and inflammatory cells, respectively. Here, we investigated if reproterol can also act in rat mast cells in vitro to facilitate the inhibitory action of disodium cromoglycate (DSCG) on histamine secretion induced by compound 48/80. Reproterol was as potent as DSCG to inhibit histamine release in rat mast cells (32.8+/-6.0 vs. 36.7+/-6.2% at 1 microM of each compound, n=10 and n=8 respectively). Mast cell stabilization by DSCG (1-100 microM) was strongly and significantly enhanced in the presence of a fixed saturating concentration of reproterol (100 microM). Conversely, the combination of DSCG (1-100 microM) with the beta2-agonist used as reference compound, salbutamol (100 microM) did not inhibit histamine release more than DSCG alone. In combination with a saturating concentration of DSCG (100 microM), reproterol inhibited histamine release more than reproterol alone. The potent Adenylate Cyclase stimulator forskolin (50 microM) was able to inhibit histamine release to a similar extent as DSCG and significantly (P<0.05) enhanced the inhibition of histamine release by DSCG. Finally, the phosphodiesterase inhibitor theophylline (100 microM) was equipotent to reproterol and DSCG in stabilizing rat mast cells. In conclusion, reproterol enhances the ability of disodium cromoglycate to stabilize rat mast cells. This effect is not shared by salbutamol and can be, at least in part, independent of beta2-adrenoceptor stimulation.