Rapid activation of basolateral potassium transport in human colon by oestradiol

Abstract

1 We investigated the eect of oestradiol on basolateral potassium channels in human colonic epithelium. 2 Ion transport was quanti®ed 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 quanti®ed using spectro¯ouresence techniques. 3 Experiments were performed with either 10 nM or 1 mM 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 (DI K =11.2+1.2 mA.cm 72 , n=6). This response was prevented by treatment of the serosal membrane with tolbutamide (1 mM). With 1 mM Ca 2+ in the apical bathing solution addition of oestradiol produced a rapid fall in current (DI K =712.8+1.4 mA.cm 72 ), this response was prevented by treatment of the basolateral membrane with tetra-pentylammonium (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; P50.01). 6 These results suggest that oestradiol rapidly modulates serosal K transport in human colon. These eects depend upon intact Na + /H + exchange and protein kinase C. We propose a nonclassical, possibly membrane linked, mechanism for oestradiol action in human colonic epithelium.

Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon

“…Previous data from our laboratory suggest that the rapid onset of the 17-estradiol antisecretory effect is incompatible with a genomic signaling pathway associated with estrogenic action [8][9][10][11][12][13]. In this study, the effects of 17-estradiol on enterotoxin-induced Cl (Fig.…”

“…Previous studies have shown that physiological concentrations of 17-estradiol rapidly increase intracellular Ca 2+ concentration [8,9], stimulate protein kinase C (PKC) and cAMP-dependent protein kinase (PKA) activity [10], and modulate several K + conductances in mammalian colonic epithelia [11]. We have also reported that 17-estradiol rapidly inhibits basal and forskolin-stimulated Cl -secretion in rat distal colonic epithelium through inhibition of basolateral KCNQ1 channels [12,13].…”

Capsaicin induces NKCC1 internalization and inhibits chloride secretion in colonic epithelial cells independently of TRPV1

“…To test whether capsaicin affects chloride secretion in mouse colon, proximal and distal colon were mounted in Ussing chambers and the short-circuit current (I sc ) was monitored. In the colon, the I sc elicited by an increase of intracellular cAMP is mainly due to chloride secretion (38). Forskolin (FSK) was used here to activate adenylate cyclase and increase intracellular cAMP content.…”

“…Because excessive activation of chloride secretion underlies diarrheal disorders, substances that inhibit this process are of interest for targeted pharmacotherapy. Inhibition of chloride secretion can be accomplished at different levels such as blockade of apical chloride channels (43), blockade of basolateral potassium channels (38,39) and internalization of NKCC1 (11,58). Various natural compounds produced by luminal bacteria such as short-chain fatty acids and ammonium ions can inhibit chloride secretion (47,66).…”

Rapid responses to aldosterone in the kidney and colon

“…This change in intracellular pH has a significant impact on basolateral K + conductances producing activation of K + ATP channels and inhibition of a calciumdependent potassium channel (K + Ca ) [72,15]. Previous studies have demonstrated that K ATP channels are involved in electrogenic Na + absorption in distal colon [72,74,75]. These results suggest that aldosterone's non-genomic action would lead to a rapid increase in Na + absorption.…”