Correlation of cyclic AMP accumulation and relaxant actions of salmeterol and salbutamol in bovine tracheal smooth muscle

Abstract

1. The ability of salmeterol to stimulate cyclic AMP accumulation and relaxation has been compared with that of salbutamol in bovine tracheal smooth muscle. In addition, the anti-spasmogenic effects of these agents and their abilities to modulate histamine-stimulated [3H]-inositol phosphate accumulation have also been investigated. 2. In tissue strips, a close temporal correlation was found to exist between salmeterol (0.1 microM)-induced relaxation of methacholine (500 nM)-induced tone and cyclic AMP accumulation, both maximal reversal of induced tone (26.2 +/- 6.0%) and maximal levels of cyclic AMP accumulation being achieved after 30-40 min. In contrast to salmeterol, salbutamol exerted greater and more rapid effects on both parameters. Maximal reversal of methacholine-induced tone (79.3 +/- 14.0%) and maximal levels of cyclic AMP accumulation were produced within 5 min. 3. Salmeterol-induced cyclic AMP accumulation (EC50 = 5.3 [1.8 - 15.2] nM) and inhibition of histamine (0.1 mM)-stimulated [3H]-inositol phosphate accumulation (IC50 = 1.4 [0.3-6.3] nM) were both more potent than those induced by salbutamol (EC50 = 169 [99 - 290] nM; IC50 = 13.8 [7.0 - 27.4] nM). However, maximal effects exerted by each of these agents were similar in magnitude. 4. Anti-spasmogenic effects were examined by beta-adrenoceptor agonist application to tissue strips prior to construction of spasmogen concentration-effect curves. Both salmeterol and salbutamol exerted more marked inhibition of the contractile response induced by histamine than that induced by methacholine, salmeterol being the more potent agent, while salbutamol produced a greater maximal inhibitory effect. 5. The results demonstrate that salmeterol is a more potent agent than salbutamol and have highlighted a close temporal correlation between promotion of cyclic AMP accumulation and tissue relaxation stimulated by each agent when both parameters are measured under identical conditions.