The underlying cellular mechanism in the effect of tetramethylpyrazine on the anion secretion of colonic mucosa.
The present study investigated the underlying cellular mechanism in the effect of ligustrazine (tetramethylpyrazine, TMP) on the anion secretion of colonic mucosa in rats using a short-circuit current (I(sc)) technique in conjunction with "tool drugs." (i) After a pretreatment of the tissues by bathing the bilateral surface with Cl(-)-free Krebs-Henseleit (K-H) solution for over an hour, a basolateral application of 1 mmol/l TMP produced an increase in I(sc), and the total charges transported for 30 min were about 8.7 +/- 1.4 mC/cm(2); an apical pretreatment of DPC and a basolateral addition of acetazolamide decreased the TMP-induced I(sc) by about 60% (P < 0.01) and 45% (P < 0.05), respectively; a basolateral application of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), the inhibitor of Na(+)-HCO(3)(-) cotransporter (NBC), did not alter the TMP-induced I(sc). (ii) After the bilateral surface of mucosa was bathed with HCO(3)(-)-free K-H solution for over an hour, a basolateral application of 1 mmol/l TMP produced an increase in I(sc), and the total charges transported in 30 min were about 8.3 +/- 1.9 mC/cm(2); an apical pretreatment of DPC (1 mmol/l), the inhibitor of Cl(-) channels, decreased the TMP-induced Isc by about 84% (P < 0.01). The basolateral presence of bumetanide (0.1 mmol/l), the inhibitor of Na(+)-K(+)-Cl(-) cotransporter (NKCC), significantly reduced the TMP-evoked I(sc) by about 86% (P < 0.01). In conclusion, (i) ligustrazine could promote colonic mucosa secretion Cl(-) via apical Cl(-) channels and basolateral NKCC; (ii) ligustrazine could promote colonic mucosa secretion HCO(3)(-) via apical Cl(-) channels and the basolateral diffusion of CO(2).
Zhao
Wen-Chao
WC
Department of Physiology, Medical School, Zhengzhou University, Zhengzhou 450052, Henan Province, China.
Duan
Dong-Xiao
DX
Wang
Zhi-Ju
ZJ
Tang
Ning
N
Yan
Ming
M
Zhang
Gui-Hong
GH
Xing
Ying
Y
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002034:Bumetanide / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D004558:Electric Stimulation; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D049994:Sodium Potassium Chloride Symporter Inhibitors; D027982:Sodium-Bicarbonate Symporters / Q000037:antagonists & inhibitors; D028021:Sodium-Potassium-Chloride Symporters / Q000187:drug effects / Q000502:physiology; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D001639:Bicarbonates; D002121:Calcium Channel Blockers; D018118:Chloride Channels; D002712:Chlorides; D011719:Pyrazines; D049994:Sodium Potassium Chloride Symporter Inhibitors; D027982:Sodium-Bicarbonate Symporters; D028021:Sodium-Potassium-Chloride Symporters; D062367:ortho-Aminobenzoates; D002034:Bumetanide; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002245:Carbon Dioxide; C001209:fenamic acid; D000086:Acetazolamide; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; C017953:tetramethylpyrazine