title: Zinc inhibits cAMP-stimulated Cl secretion via basolateral K-channel blockade in rat ileum.
abstract: Zn, an essential micronutrient and second most abundant trace element in cell and tissues, reduces stool output when administered to children with acute diarrhea. The mechanism by which Zn improves diarrhea is not known but could result from stimulating Na absorption and/or inhibiting anion secretion. The aim of this study was to investigate the direct effect of Zn on intestinal epithelial ion absorption and secretion. Rat ileum was partially stripped of serosal and muscle layers, and the mucosa was mounted in lucite chambers. Potential difference and short-circuit current were measured by conventional current-voltage clamp method. 86Rb efflux and uptake were assessed for serosal K channel and Na-K-2Cl cotransport activity, respectively. Efflux experiments were performed in isolated cells preloaded with 86Rb in the presence of ouabain and bumetanide, whereas uptake experiments were performed in low-Cl isotonic buffer containing Ba and ouabain. Neither mucosal nor serosal Zn affected glucose-stimulated Na absorption. In contrast, forskolin-induced Cl secretion was markedly reduced by serosal but not mucosal addition of Zn. Zn also substantially reversed the increase in Cl secretion induced by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) with half-maximal inhibitory concentration of 0.43 mM. In contrast, serosal Zn did not alter Cl secretion stimulated by carbachol, a Ca-dependent agonist. Zn inhibited 8-BrcAMP-stimulated 86Rb efflux but not carbachol-stimulated 86Rb efflux. Zn had no effect on bumetanide-sensitive 86Rb uptake, Na-K-ATPase, or CFTR. We conclude from these studies that Zn inhibits cAMP-induced Cl secretion by blocking basolateral membrane K channels.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, 333 Cedar St., New Haven, Connecticut 06520, USA.
authors.forename: Kazi Mirajul
authors.initials: KM
authors.lastname: Hoque
authors.forename: Vazhaikkurichi M
authors.initials: VM
authors.lastname: Rajendran
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Binder
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000737:chemistry; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000502:physiology*; D003967:Diarrhea / Q000503:physiopathology; D020895:Enterocytes / Q000187:drug effects / Q000502:physiology*; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D009004:Monosaccharide Transport Proteins / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000502:physiology; D051269:Sodium-Glucose Transporter 1; D028021:Sodium-Potassium-Chloride Symporters / Q000502:physiology; D064506:Solute Carrier Family 12, Member 2; D013997:Time Factors; D015032:Zinc / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D015221:Potassium Channels; C578879:Slc12a2 protein, rat; D051269:Sodium-Glucose Transporter 1; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D001464:Barium; D002217:Carbachol; D012964:Sodium; D000242:Cyclic AMP; D015032:Zinc