Spasmolytic effect of caulerpine involves blockade of Ca2+ influx on guinea pig ileum

Abstract

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 Emax 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 (CaV), since caulerpine slightly inhibited the CaCl 2-induced contractions in depolarizing medium without Ca 2+, shifting the curves to the right and with Emax reduction. According to these results, the spasmolytic effect of caulerpine on guinea pig ileum seems to involve inhibition of Ca2+ influx through CaV. However, other mechanisms are not discarded. © 2013 by the authors; licensee MDPI.