Dopamine stimulates Cl(-) absorption coupled with HCO(3)(-) secretion in rat late distal colon.
Freshly isolated rat colonic mucosa close to anus (the late distal colonic mucosa) was used to investigate the effect of dopamine on the rat late distal colonic ion transport by means of short-circuit current (I(SC)) recording and reverse transcription PCR (RT-PCR) analysis. The results showed that the basolateral addition of dopamine (0.1-1000 micromol/l) produced a concentration-dependent downward deflection in I(SC) with an apparent EC(50) of 20.06 micromol/l in the late distal colon. The dopamine-induced I(SC) decrease was abolished by bilateral removal of Cl(-) or HCO(3)(-), apical Cl(-) replacement and apical pretreatment with non-specific Cl(-) channel blocker/transporter inhibitor, DPC (1 mmol/l) or glibenclamide (1 mmol/l), and reversed by subsequent addition of glibenclamide. Removal of basolateral Na(+) or reducing basolateral HCO(3)(-) (3 mmol/l) as well as basolateral pretreatment with DIDS (4,4'-didsothio- cyanostilbene-2, 2'-disulfonic acid) (250 micromol/l), an inhibitor of NBC or AE, could also inhibit the dopamine-induced I(SC) response. However, apical pretreatment with epithelial Na(+) channel blocker, amiloride (10 micromol/l), Ca(2+)-dependent Cl(-) channel blocker/anion exchanger, DIDS (100 micromol/l), or putative K(+) blockers such as Ba(2+) (5 mmol/l), TEA (tetraethylammonium) (5 mmol/l) or 293B (trans-6-cyano-4- (N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chromane) (10 micromol/l) did not significantly affect the dopamine-induced I(SC) response. RT-PCR results showed the expression of anion exchanger, SLC26A3, but not SLC26A6, in rat late distal colon. In conclusion, the present results suggest that dopamine may promote rat late distal colonic epithelial Cl(-) absorption coupled with HCO(3)(-) secretion, which may be mediated by apical electrogenic anion exchanger, SLC26A3, and require basolateral entry of HCO(3)(-) through Na(+)-HCO(3)(-) cotransporter. The present findings reveal a previously unreported dopamine-regulated anion transport process in rat late distal colon, which may have implication in Parkinson's disease.
Zhang
Gui Hong
GH
Epithelial Cell Biology Research Center, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, PR China.
Zhu
Jin Xia
JX
Xue
Hong
H
Fan
Jing
J
Chen
Xin
X
Tsang
Lai Ling
LL
Chung
Yiu Wa
YW
Xing
Ying
Y
Chan
Hsiao Chang
HC
D000818:Animals; D017920:Antiporters / Q000235:genetics; D001639:Bicarbonates / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010300:Parkinson Disease / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000076988:Sulfate Transporters
D017920:Antiporters; D001639:Bicarbonates; D002712:Chlorides; D012333:RNA, Messenger; C489861:Slc26a3 protein, rat; D000076988:Sulfate Transporters; D004298:Dopamine