title: 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 CaCl₂-induced contractions in depolarizing medium without Ca²⁺, 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.
authors.affiliation: Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceió 57020-720, AL, Brazil. luiz0710@gmail.com
authors.forename: Luiz Henrique Agra
authors.initials: LH
authors.lastname: Cavalcante-Silva
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Carvalho Correia
authors.forename: José Maria
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.forename: Bagnólia Araújo
authors.initials: BA
authors.lastname: da Silva
authors.forename: Bárbara Viviana
authors.initials: BV
authors.lastname: de Oliveira Santos
authors.forename: Daysianne Pereira
authors.initials: DP
authors.lastname: de Lira
authors.forename: Jéssica Celestino Ferreira
authors.initials: JC
authors.lastname: Sousa
authors.forename: George Emmanuel C
authors.initials: GE
authors.lastname: de Miranda
authors.forename: Fabiana
authors.initials: F
authors.lastname: de Andrade Cavalcante
authors.forename: Magna Suzana
authors.initials: MS
authors.lastname: Alexandre-Moreira
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D046068:Caulerpa / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D007211:Indoles; D010276:Parasympatholytics; C000392:caulerpin; D012701:Serotonin; D006632:Histamine; D002217:Carbachol; D002118:Calcium