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Epithelial Cell Specific Capsaicin Effect on Cl − secretion and NKCC1
Author(s) -
Jacobs Jeremy M,
FedorChaiken Mary,
Merk Lisa M,
Delpire Eric,
Matthews Jeffrey B,
Worrell Roger T
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a542
Subject(s) - capsaicin , internalization , secretion , chemistry , extracellular , forskolin , trpv1 , resiniferatoxin , receptor , medicine , pharmacology , endocrinology , microbiology and biotechnology , biology , biochemistry , transient receptor potential channel
Capsaicin concentrations well within the physiologic effective dose can be achieved in gut thus exposing the mucosa to this potential signaling molecule. Capsaicin effects on gut thus far have been attributed to a neuronal action. Since capsaicin treatment results in increased [Ca 2+ ] i via action on TRPV1 receptors in neurons, this study sought to determine if capsaicin has a direct effect on epithelial cells. In colonic T84 cells, Ca ++ ‐agonist pretreatment results in attenuation of subsequent cAMP‐stimulated Cl − secretion. We have previously shown that this may, in‐part, be explained by Ca ++ ‐induced internalization NKCC1. In T84, 5 min pre‐application of 2μM capsaicin resulted in an attenuated response to forskolin‐induced current similar to that obtained with pre‐application of 100 μM CCh. Capsaicin IC 50 was ~16 μM which is roughly equivalent to a mild pepper. In MDCK cells transfected with EGFP‐NKCC1, Capsaicin (15–80μM) induced visible internalization of EGFP‐NKCC1 within 5 min. Apical capsaicin induced NKCC1 internalization, whereas basolateral capsaicin was ineffective. Capsaicin‐induced NKCC1 internalization was dependent on the presence of extracellular Ca ++ . These data support direct epithelial cell capsaicin effects on gut Cl − secretion. Thus, capsaicin may be useful to limit Cl − secretion and possibly promote HCO 3 − secretion via internalization of NKCC1. Supported by NIH DK48010.