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

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 x 10(-5) M), histamine (IC50 = 1.3 +/- 0.3 x 10(-4) M) and serotonin (IC50 = 8.0 +/- 1.4 x 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 x 10(-5) M) and carbachol (EC50 = 4.6 +/- 0.7 x 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.