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Protective effect of melatonin on Ca 2+ homeostasis and contractility in acute cholecystitis
Author(s) -
GomezPinilla Pedro J.,
Camello Pedro J.,
Pozo María J.
Publication year - 2008
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2007.00520.x
Subject(s) - melatonin , contractility , medicine , endocrinology , homeostasis , calcium metabolism , chemistry , calcium
Abstract: Impaired Ca 2+ homeostasis and smooth muscle contractility co‐exist in acute cholecystitis (AC) leading to gallbladder dysfunction. There is no pharmacological treatment for this pathological condition. Our aim was to evaluate the effects of melatonin treatment on Ca 2+ signaling pathways and contractility altered by cholecystitis. [Ca 2+ ] i was determined by epifluorescence microscopy in fura‐2 loaded isolated gallbladder smooth muscle cells, and isometric tension was recorded from gallbladder muscle strips. Malondialdehyde (MDA) and reduced glutathione (GSH) contents were determined by spectrophotometry and cycloxygenase‐2 (COX‐2) expression was quantified by western blot. Melatonin was tested in two experimental groups, one of which underwent common bile duct ligation for 2 days and another that was later de‐ligated for 2 days. Inflammation‐induced impairment of Ca 2+ responses to cholecystokinin and caffeine were recovered by melatonin treatment (30 mg/kg). This treatment also ameliorated the detrimental effects of AC on Ca 2+ influx through both L‐type and capacitative Ca 2+ channels, and it was effective in preserving the pharmacological phenotype of these channels. Despite its effects on Ca 2+ homeostasis, melatonin did not improve contractility. After de‐ligation, Ca 2+ influx and contractility were still impaired, but both were recovered by melatonin. These effects of melatonin were associated to a reduction of MDA levels, an increase in GSH content and a decrease in COX‐2 expression. These findings indicate that melatonin restores Ca 2+ homeostasis during AC and resolves inflammation. In addition, this indoleamine helps in the subsequent recovery of functionality.