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17β‐Oestradiol acutely regulates Cl − secretion in rat distal colonic epithelium
Author(s) -
Condliffe Steven B.,
Doolan Christina M.,
Harvey Brian J.
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0047m.x
Subject(s) - forskolin , endocrinology , medicine , protein kinase c , secretion , secretagogue , chemistry , intracellular , chelerythrine , amiloride , prostaglandin e2 , ionomycin , epithelium , ion transporter , biology , signal transduction , stimulation , biochemistry , sodium , genetics , organic chemistry , membrane
1 In this study we used the short circuit current (I SC ) technique to measure the non‐genomic effects of the female sex steroid 17β‐oestradiol (E 2 ) on electrogenic transepithelial ion transport in rat distal colonic epithelium. 2 Basal I SC was largely composed of a transepithelial Cl − secretory component with minimal electrogenic Na + movement. E 2 (1‐100 n m ) caused a significant decrease in basal I SC after 15 min. In addition, pre‐treating colonic epithelial tissues with E 2 (0.1‐100 n m ) for 10 min significantly reduced forskolin (20 μ m )‐induced Cl − secretion. E 2 also down‐regulated Cl − secretion which was pre‐stimulated by forskolin. Cl − secretory responses to the Ca 2+ ‐dependent secretagogue carbachol (10 μ m ) were also significantly reduced in the presence of E 2 (10‐ 100 n m ). However, E 2 had no effect on amiloride‐sensitive Na + absorption. 3 The rapid anti‐secretory effect of E 2 was abolished in the presence of the intracellular Ca 2+ chelator BAPTA (50 μ m ) or the protein kinase C (PKC) inhibitor chelerythrine chloride (1 μ m ). However, in the presence of the nuclear oestrogen receptor antagonist tamoxifen (10 μ m ), E 2 still produced an inhibition of Cl − secretion. Testosterone, progesterone and 17α‐oestradiol had no significant effect on colonic Cl − secretion. Also, E 2 (100 n m ) did not alter Cl − secretion in colonic epithelia isolated from male rats. 4 We conclude that E 2 inhibits colonic Cl − secretion via a non‐genomic pathway that involves intracellular Ca 2+ and PKC. It is possible that this gender‐specific mechanism contributes to the salt and water retention associated with high E 2 states.