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- Title
Antispasmodic effects of a new kaurene diterpene isolated from Croton argyrophylloides on rat airway smooth muscle.
- Authors
Aguiar, Liza Araújo; Porto, Romulo Sousa; Lahlou, Saad; Ceccatto, Vânia Marilande; Barbosa, Roseli; Lemos, Telma Leda Gomes; dos Santos, Hélcio Silva; Coelho-de-Souza, Andrelina Noronha; Magalhães, Pedro Jorge Caldas; Zin, Walter Araújo; Leal-Cardoso, José Henrique
- Abstract
Objectives The 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. Methods Tracheae were removed and cut into two-cartilage segments that were mounted in organ baths containing Tyrode's solution. Results TCCA 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 µ m) induced contraction, but with slight potency. Conclusions TCCA 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+.
- Subjects
ANTISPASMODICS; DITERPENES; AIRWAY (Anatomy); SMOOTH muscle; CROTON (Genus)
- Publication
Journal of Pharmacy & Pharmacology, 2012, Vol 64, Issue 8, p1155
- ISSN
0022-3573
- Publication type
Article
- DOI
10.1111/j.2042-7158.2012.01494.x