title: The underlying cellular mechanism in the effect of tetramethylpyrazine on the anion secretion of colonic mucosa.
abstract: 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).
authors.affiliation: Department of Physiology, Medical School, Zhengzhou University, Zhengzhou 450052, Henan Province, China.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Zhao
authors.forename: Dong-Xiao
authors.initials: DX
authors.lastname: Duan
authors.forename: Zhi-Ju
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Tang
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Gui-Hong
authors.initials: GH
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Xing
mesh_terms: 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
chemical_list: 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