Berberine inhibition of electrogenic ion transport in rat colon.
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 microM) 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 microM) 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 microM). 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.
Taylor
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Department of Pharmacology, University College Dublin, Belfield, Ireland.
Baird
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D001599:Berberine / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D004768:Enterotoxins / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D029968:Escherichia coli Proteins; D066298:In Vitro Techniques; D007477:Ions; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012636:Secretory Rate / Q000187:drug effects; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D001427:Bacterial Toxins; D002712:Chlorides; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007477:Ions; D013729:Terpenes; C034151:heat stable toxin (E coli); D001599:Berberine; D005576:Colforsin; D015638:Cytochalasin D; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019284:Thapsigargin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D006152:Cyclic GMP