RESUMO
Previously, we demonstrated that caulerpine has spasmolytic effect on guinea pig ileum. The aim of this study was to investigate pathways of its spasmolytic action. We test caulerpine against phasic contractions induced by carbachol in the circular layer of guinea pig ileum and this alkaloid did not inhibit these contractions, indicating that caulerpine did not interfering with the mobilisation of Ca2+ from intracellular stores. Additionally, the spasmolytic effect of caulerpine did not involve K+ channels. Furthermore, we observed that α2-adrenergic receptors were not involved in the spasmolytic effect of caulerpine, since the relaxation curve induced by caulerpine was not shifted in the presence of yohimbine (α2-adrenergic antagonist). However, in the presence of propranolol (ß-adrenergic antagonist), the relaxation curve induced by caulerpine was right-shifted, resulting in a fivefold increase in EC50. Thus, a possible mechanism for the spasmolytic action of caulerpine is the activation of ß-adrenergic receptors.
RESUMO
In previous works we showed that oral administration of caulerpine, a bisindole alkaloid isolated from algae of the genus Caulerpa, produced antinociception when assessed in chemical and thermal models of nociception. In this study, we evaluated the possible mechanism of action of this alkaloid in mice, using the writhing test. The antinociceptive effect of caulerpine was not affected by intraperitoneal (i.p.) pretreatment of mice with naloxone, flumazenil, l-arginine or atropine, thus discounting the involvement of the opioid, GABAergic, l-arginine-nitric oxide and (muscarinic) cholinergic pathways, respectively. In contrast, i.p. pretreatment with yohimbine, an α2-adrenoceptor antagonist, or tropisetron, a 5-HT3 antagonist, significantly blocked caulerpine-induced antinociception. These results suggest that caulerpine exerts its antinociceptive effect in the writhing test via pathways involving α2-adrenoceptors and 5-HT3 receptors. In summary, this alkaloid could be of interest in the development of new dual-action analgesic drugs.
Assuntos
Alcaloides/administração & dosagem , Indóis/administração & dosagem , Dor Nociceptiva/tratamento farmacológico , Medição da Dor , Alcaloides/química , Analgésicos/administração & dosagem , Animais , Humanos , Indóis/química , Camundongos , Naloxona/administração & dosagem , Óxido Nítrico/metabolismo , Dor Nociceptiva/metabolismo , Dor Nociceptiva/patologia , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Receptores Adrenérgicos alfa 2/metabolismo , Receptores 5-HT3 de Serotonina/efeitos dos fármacos , Receptores 5-HT3 de Serotonina/metabolismo , Tropizetrona , Ioimbina/administração & dosagemRESUMO
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 × 10â»5 M), histamine (IC50 = 1.3 ± 0.3 × 10â»4 M) and serotonin (IC50 = 8.0 ± 1.4 × 10â»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 × 10â»5 M) and carbachol (EC50 = 4.6 ± 0.7 × 10â»5 M) in a concentration-dependent manner. This effect was probably due to inhibition of Ca²âº influx through voltage-gated calcium channels (CaV), since caulerpine slightly inhibited the CaCl2-induced contractions in depolarizing medium without Ca²âº, 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 Ca²âº influx through CaV. However, other mechanisms are not discarded.