Berberine inhibition of electrogenic ion transport in rat colon

摘要

1 The effects of the alkaloid berberine on basal and stimulated ion transport were investigated in voltage-clamped rat colonic epithelia. 2 Berberine (100-500 μM) reduced basal short circuit current (SCC) when applied basolaterally but not when applied apically. 3 SCC responses to mast cell activation by anti-rat IgE were significantly attenuated in the presence of berberine. 4 Berberine, applied to the basolateral bathing solution, also reduced SCC responses to the following agents which stimulate chloride secretion in rat colon: carbachol, forskolin, sodium nitroprusside, dibutyryl cyclic-AMP, heat-stable E. coli enterotoxin, 8-bromo-cyclic GMP and thapsigargin. Calcium mediated ion transport responses appear to be more sensitive to berberine inhibition than those which are cyclic GMP-mediated, which in turn are more sensitive than cyclic AMP-mediated responses. 5 Berberine added apically was without effect upon forskolin-stimulated ion transport. Cytochalasin D treatment of the lumenal surface of rat colon conferred apical-side sensitivity to berberine. 6 Berberine (at concentrations up to 500 μM) was without effect on generation of cyclic AMP by forskolin or on generation of cyclic GMP by sodium nitroprusside in isolated mucosal segments. Protein kinase A activity stimulated by dibutyryl cyclic AMP was unaffected by berberine (at concentrations up to 500 μM). 7 The precise mechanism of action of berberine remains to be elucidated. However, its site of action appears to be distal to second messenger production and may be at a level common to all stimuli of colonic chloride secretion.