Spasmolytic Effect of Caulerpine Involves Blockade of Ca2+ Influx on Guinea Pig Ileum

摘要

In this work, we investigated the spasmolytic effect of caulerpine, a bisindole alkaloid isolated from marine algae of the Caulerpa genus, on guinea pig ileum. Our findings indicated that caulerpine inhibited phasic contractions induced by carbachol (IC₅₀ = 7.0 ± 1.9 × 10−5 M), histamine (IC₅₀ = 1.3 ± 0.3 × 10−4 M) and serotonin (IC₅₀ = 8.0 ± 1.4 × 10−5 M) in a non-selective manner. Furthermore, caulerpine concentration-dependently inhibited serotonin-induced cumulative contractions (pD′₂ = 4.48 ± 0.08), shifting the curves to the right with E_max reduction and slope of 2.44 ± 0.21, suggesting a noncompetitive antagonism pseudo-irreversible. The alkaloid also relaxed the ileum pre-contracted by KCl (EC₅₀ = 9.0 ± 0.9 × 10−5 M) and carbachol (EC₅₀ = 4.6 ± 0.7 × 10−5 M) in a concentration-dependent manner. This effect was probably due to inhibition of Ca2+ influx through voltage-gated calcium channels (Ca_V), since caulerpine slightly inhibited the CaCl₂-induced contractions in depolarizing medium without Ca2+, shifting the curves to the right and with E_max reduction. According to these results, the spasmolytic effect of caulerpine on guinea pig ileum seems to involve inhibition of Ca2+ influx through Ca_V. However, other mechanisms are not discarded.