Palmatine, a protoberberine alkaloid, inhibits both Ca(2+)- and cAMP-activated Cl(-) secretion in isolated rat distal colon.
OBJECTIVE
The protoberberine alkaloid berberine has been reported to inhibit colonic Cl(-) secretion. However, it is not known if other protoberberine alkaloids share these effects. We have therefore selected another protoberberine alkaloid, palmatine, to assess its effects on active ion transport across rat colonic epithelium.


METHODS
Rat colonic mucosa was mounted in Ussing chambers and short circuit current (I (SC)), apical Cl(-) current and basolateral K(+) current were recorded. Intracellular cAMP content was determined by an enzyme immunoassay. Intracellular Ca(2+) concentration was measured with Fura-2 AM.


RESULTS
Palmatine inhibited carbachol-induced Ca(2+)-activated Cl(-) secretion and the carbachol-induced increase of intracellular Ca(2+) concentration. Palmatine also inhibited cAMP-activated Cl(-) secretion induced by prostaglandin E(2) (PGE(2)) or forskolin. Palmatine prevented the elevation of intracellular cAMP by forskolin. Determination of apical Cl(-) currents showed that palmatine suppressed the forskolin-stimulated, apical cAMP-activated Cl(-) current but not the carbachol-stimulated apical Ca(2+)-activated Cl(-) current. Following permeabilization of apical membranes with nystatin, we found that palmatine inhibited a carbachol-stimulated basolateral K(+) current that was sensitive to charybdotoxin and resistant to chromanol 293B. However, the forskolin-stimulated basolateral K(+) current inhibited by palmatine was specifically blocked by chromanol 293B and not by charybdotoxin.


CONCLUSIONS
Palmatine attenuated Ca(2+)-activated Cl(-) secretion through inhibiting basolateral charybdotoxin-sensitive, SK4 K(+) channels, whereas it inhibited cAMP-activated Cl(-) secretion by inhibiting apical CFTR Cl(-) channels and basolateral chromanol 293B-sensitive, KvLQT1 K(+) channels.
Wu
D Z
DZ
Laboratory of Pharmacology, Institute of Chinese Materia Medica, Shanghai University of TCM, Shanghai, PR China.
Yuan
J Y
JY
Shi
H L
HL
Hu
Z B
ZB
D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D018999:Charybdotoxin / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D001600:Berberine Alkaloids; D002712:Chlorides; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin; D000242:Cyclic AMP; C005413:palmatine; D002118:Calcium