ABSTRACT
We have characterized the actions of ApC, a sea anemone polypeptide toxin isolated from Anthopleura elegantissima, on neuronal sodium currents (I(Na)) using current and voltage-clamp techniques. Neurons of the dorsal root ganglia of Wistar rats (P5-9) in primary culture were used for this study. These cells express tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) I(Na). In current-clamp experiments, application of ApC increased the average duration of the action potential. Under voltage-clamp conditions, the main effect of ApC was a concentration-dependent increase in the TTX-S I(Na) inactivation time course. No significant effects were observed on the activation time course or on the current peak-amplitude. ApC also produced a hyperpolarizing shift in the voltage at which 50% of the channels are inactivated and caused a significant decrease in the voltage dependence of Na+ channel inactivation. No effects were observed on TTX-R I(Na). Our results suggest that ApC slows the conformational changes required for fast inactivation of the mammalian Na+ channels in a form similar to other site-3 toxins, although with a greater potency than ATX-II, a highly homologous anemone toxin.
Subject(s)
Cnidarian Venoms/pharmacology , Neurons/drug effects , Neurotoxins/pharmacology , Peptides/pharmacology , Sea Anemones/chemistry , Sodium Channels/physiology , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Electric Stimulation , Female , Ganglia, Spinal/cytology , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Membrane Potentials/radiation effects , Neurons/classification , Patch-Clamp Techniques/methods , Rats , Rats, Wistar , Sodium Channel Blockers/pharmacology , Tetrodotoxin/pharmacologyABSTRACT
Marine organisms represent a valuable source of new compounds. The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new active substances in the field of the development of bioactive products. In this paper, the molecular diversity of different marine peptides is described as well as information about their biological properties and mechanisms of action is provided. Moreover, a short review about isolation procedures of selected bioactive marine peptides is offered. Novel peptides from sponges, ascidians, mollusks, sea anemones and seaweeds are presented in association with their pharmacological properties and obtainment methods.
Subject(s)
Marine Biology , Peptides/isolation & purification , Peptides/pharmacology , Amino Acid Sequence , Animals , Molecular Sequence Data , Peptides/chemistry , Sequence Homology, Amino AcidABSTRACT
Se estudió la distribución biológica del extracto ácido acético-acetónico de Bunodosoma granulífera. Se analizó la afectación de la biodistribución de los polipéptidos radioiodados en función de la pureza radioquímica, la dosis y el tiempo, previa inyección i.p. en ratones. La detección de radioactividad en el cerebro, a partir de los 5 min de inyectado el animal, permite suponer la posible acción del veneno en el sistema nervioso central.
Subject(s)
Mice , Animals , Biotransformation , Marine Toxins/metabolism , Sea Anemones , Blood-Brain Barrier , Cerebellum/analysis , Cerebellum/metabolism , Cerebrum/analysis , Cerebrum/metabolism , Cnidaria , Cuba , Liver/analysis , Liver/metabolism , Marine Toxins/pharmacokinetics , Iodine Radioisotopes/metabolism , Iodine Radioisotopes , Kidney/analysis , Kidney/metabolismABSTRACT
Se estudió la distribución biológica del extracto ácido acético-acetónico de Bunodosoma granulífera. Se analizó la afectación de la biodistribución de los polipéptidos radioiodados en función de la pureza radioquímica, la dosis y el tiempo, previa inyección i.p. en ratones. La detección de radioactividad en el cerebro, a partir de los 5 min de inyectado el animal, permite suponer la posible acción del veneno en el sistema nervioso central. (AU)