The Effect of Forskolin on Isoproterenol-Induced Relaxation in Rat and Guinea-Pig Tracheal Preparations

Abstract

Objective: In this study, we have examined the relaxant effects of forskolin and isoproterenol on isolated rings of the rat and guinea-pig trachea. The objective of the study was to compare the potency and efficacy of both agents on the tracheal preparations from different species and to assess any possible synergistic bronchodilator effect of forskolin and isoproterenol. Method: The preparations were mounted in organ baths containing Krebs-Henseleit solution and changes in isometric tension were recorded. Results: Forskolin, an activator of adenylate cyclase, and the β-adrenergic stimulator isoproterenol produced concentration-dependent (10^–9 to 3 × 10^–5 M) relaxations in rat and guinea-pig tracheal rings pre-contracted by carbachol (10^–6 and 3 × 10^–7 M, respectively). Forskolin was less potent than isoproterenol but is had a higher relaxing efficacy. It increased isoproterenol-elicited maximal relaxation in rat tracheal preparations. Forskolin significantly potentiated the bronchorelaxant response to isoproterenol in guinea-pig preparations (lower IC₅₀ values). Moreover, relaxation to standard concentrations of isoproterenol (10^–8 and 3 × 10^–8 M) were significantly enhanced in the presence of forskolin (10^–6 and 3 × 10^–6 M) in both rat and guinea-pig tracheal rings. Conclusion: These results suggest that in guinea-pig tracheal ring preparations, forskolin produces an apparent potentiation of isoproterenol-induced relaxation, while in rat tracheal preparations, forskolin increases the efficacy of isoproterenol. This response could provide an alternative to increasing the dosage of β-adrenergic bronchodilator drugs in patients with asthma. Therefore, a combined therapy with forskolin may be considered.