XANTATINA INHIBE LA ACTIVACIÓN DE MASTOCITOS INDUCIDA POR NEUROPÉPTIDOS PRO-INFLAMATORIOS
DOI:
https://doi.org/10.31051/1852.8023.v2.n1.13859Palabras clave:
Xanthanólido, sustancia P, neurotensina, xanthanolide, substance P, neurotensinResumen
Los mastocitos son células del tejido conectivo que participan en la génesis y modulación de las respuestas inflamatorias. Previamente hemos demos-trado que xanthatina (xanthanólido sesquiterpeno aislado de Xanthium cavanillesii Schouw) inhibe la activación de mastocitos inducida por secretagogos experimentales. Sin embargo, se desconoce su efecto sobre la activación de mastocitos inducida por estímulos fisiopatológicos. Estos estímulos incluyen, entre otros, los neuropéptidos pro-inflamatorios sustancia P y neurotensina, responsables de una de las principales vías de inflamación neurogénica. El objetivo del presente trabajo fue estudiar el efecto de xanthatina sobre la activación de mastocitos inducida por sustancia P y neurotensina. Mastocitos peritoneales de rata se incubaron con: 1) PBS (basal); 2) sustancia P (100 µm); 3) neurotensina (50 µm); 4) xanthatina (8-320 µm)+sustancia P; 5) xanthatina (8-320 µm)+neurotensina. Se llevaron a cabo los siguientes estudios: análisis dosis-respuesta de la liberación de serotonina inducida por neuropéptidos proinflamatorios, vitalidad celular, morfología mastocitaria por microscopía óptica y electrónica, análisis de estabilidad de xanthatina por cromatografía en capa fina. Los ensayos de liberación de serotonina y los estudios morfológicos mostraron la efectividad de xanthatina para estabilizar mastocitos. El presente estudio provee la primer evidencia a favor de la hipótesis de que xanthatina inhibe la liberación de serotonina inducida por sustancia P y neurotensina a partir de mastocitos peritoneales. Este sesquiterpeno podría representar una nueva alternativa fármacológica en la regulación de la activación mastocitaria para el tratamiento de las inflamaciones neurogénicas.
Mast cells are connective tissue cells involved in the genesis and modulation of inflammatory responses. We have previously shown that xanthatin (xanthanolide sesquiterpene isolated from Xanthium cavanillesii Schouw) inhibits mast cell activation induced by experimental secretagogues. However, the effect of xanthatin on mast cell activation induced by pathophysiological stimuli remains unknown. These stimuli include, among others, the pro-inflammatory neuropeptide substance P and neurotensin, responsible for one of the main pathways of neurogenic inflammation. The present study was designed to examine the effects of xanthatin on mast cell activation induced by pro-inflammatory peptides, such as substance P and neurotensin. Rat peritoneal mast cells were incubated with: 1) PBS (basal); 2) substance P (100 µm); 3) neurotensin (50 µm); 4) xanthatin (8-320 µm)+substance P; 5) xanthatin (8-320 µm)+neurotensin. Concentration-response studies of mast cell serotonin release evoked by pro-inflammatory neuropeptides, evaluation of mast cell viability and morphology by light and electron microscopy, and drug stability analysis by thin layer chromatography were performed. Serotonin release studies, carried out together with morphological studies, showed the effectiveness of xanthatin to stabilize mast cells. The present study provides the first strong evidence in favour of the hypothesis that xanthatin inhibits substance P - and neurotensin-induced serotonin release from peritoneal mast cells. Our findings may provide an insight into the design of novel pharmacological agents which may be used to regulate the mast cell response in neurogenic inflammation.
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