Antispasmodic effects of a new kaurene diterpene isolated from Croton argyrophylloides on rat airway smooth muscle

Abstract

AbstractObjectivesThe effects of rel-(1S,4aS,7S,8aS)-7-(1-vinyl)-tetradecahydro-1,4a-dimethylphenanthrene-7,8a-carbolactone-1-carboxylic acid (TCCA), a new ent-kaurene diterpene isolated from Croton argyrophylloides, on rat tracheal preparations were investigated.MethodsTracheae were removed and cut into two-cartilage segments that were mounted in organ baths containing Tyrode's solution.ResultsTCCA reduced the contractions induced by electrical field stimulation, relaxed K+-induced contractions, and inhibited both phasic and tonic components of the K+- and ACh-induced contractions. TCCA reduced the serotonin-induced contraction, abolished that evoked by K+ in the presence of epinephrine, and also reduced the ACh-induced contractions under Ca2+-free conditions. TCCA blocked contractions that depend on divalent cation inflow through voltage-operated Ca2+ channels (VOCCs) and receptor-operated Ca2+ channels (ROCCs), but had greater potency to block VOCC- than ROCC-dependent contractions or contractions induced by ACh in Ca2+-free conditions. TCCA relaxed the phorbol 12,13 dibutyrate (1 µm) induced contraction, but with slight potency.ConclusionsTCCA induces an antispasmodic effect through several mechanisms including blockade of either VOCCs (with greater potency) or ROCCs, blockade of IP3-induced Ca2+ release from sarcoplasmic reticulum (with intermediate potency) and reduction of the sensitivity of contractile proteins to Ca2+.