title: Rapid activation of basolateral potassium transport in human colon by oestradiol.
abstract: 1. We investigated the effect of oestradiol on basolateral potassium channels in human colonic epithelium. 2. Ion transport was quantified using short circuit current (I:(sc)) measurements of samples mounted in Ussing chambers. Serosal K transport was studied using nystatin permeabilization of the apical membrane. Intracellular pH changes were quantified using spectroflouresence techniques. 3. Experiments were performed with either 10 nM or 1 microM Ca(2+) in the apical bathing solution. With 10 nM Ca(2+) in the apical bathing solution addition of oestradiol (1 nM) to the basolateral bath produced a rapid increase in current (delta I(K)=11.2+/-1.2 microA.cm(-2), n=6). This response was prevented by treatment of the serosal membrane with tolbutamide (1 microM). With 1 microM Ca(2+) in the apical bathing solution addition of oestradiol produced a rapid fall in current (delta I(K)=-12.8+/-1.4 microA.cm(-2)), this response was prevented by treatment of the basolateral membrane with tetra-pentyl-ammonium (TPeA). These responses were rapid and occurred independently of protein synthesis. 4. Inhibition of basolateral Na(+)/H(+) exchange with either amiloride or a low sodium bathing solution prevented this response. These responses were prevented by inhibition of protein kinase C (PKC) with bis-indolyl-maleimide. 5. Oestradiol (1 nM) produced a rapid intracellular alkanization (mean increase=0.11 pH units; n=6; P<0.01). 6. These results suggest that oestradiol rapidly modulates serosal K transport in human colon. These effects depend upon intact Na(+)/H(+) exchange and protein kinase C. We propose a non-classical, possibly membrane linked, mechanism for oestradiol action in human colonic epithelium.
authors.affiliation: Department of Clinical Neurophysiology, Box 124, Addenbrookes Hospital, Cambridge, CB2 2QQ.
authors.forename: B
authors.initials: B
authors.lastname: McNamara
authors.forename: D C
authors.initials: DC
authors.lastname: Winter
authors.forename: J
authors.initials: J
authors.lastname: Cuffe
authors.forename: C
authors.initials: C
authors.lastname: Taylor
authors.forename: G C
authors.initials: GC
authors.lastname: O'Sullivan
authors.forename: B J
authors.initials: BJ
authors.lastname: Harvey
mesh_terms: D002118:Calcium / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000493:pharmacokinetics*; D015221:Potassium Channels / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012704:Serous Membrane / Q000187:drug effects / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: D004965:Estrogen Antagonists; D015221:Potassium Channels; D011500:Protein Synthesis Inhibitors; D000644:Quaternary Ammonium Compounds; D017923:Sodium-Hydrogen Exchangers; D013629:Tamoxifen; D004958:Estradiol; D014044:Tolbutamide; D003513:Cycloheximide; C027435:tetrapentylammonium; D011188:Potassium; D002118:Calcium