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The EP 3 receptor stimulates ceramide and diacylglycerol release and inhibits growth of primary keratinocytes
Author(s) -
Konger Raymond L.,
Brouxhon Sabine,
Partillo Steven,
VanBuskirk JoAnne,
Pentland Alice P.
Publication year - 2005
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2005.00381.x
Subject(s) - diacylglycerol kinase , ceramide , lipid signaling , primary (astronomy) , chemistry , microbiology and biotechnology , receptor , endocrinology , medicine , signal transduction , biology , biochemistry , protein kinase c , apoptosis , physics , astronomy
Primary human keratinocytes (PHKs) are known to express the EP 3 subtype of prostaglandin E 2 receptor. To better understand the role of EP 3 receptors in regulating epidermal function, we characterized their expression, localization, and signaling effects in human skin. Three different splice variants of the EP 3 receptor (EP 3A1 , EP 3C , and EP 3D ) were found to be expressed. Immunohistochemical analysis of human skin demonstrated that EP 3 receptors were most prominently expressed in the basal and lower spinous layers of the epidermis. The EP 3 receptor agonist sulprostone was then used to examine EP 3 receptor‐dependent keratinocyte signaling pathways and functional effects. We observed that sulprostone inhibits keratinocyte growth at doses between 0.02 and 2 nM and induces sn‐1,2‐diacylglycerol (DAG) and ceramide production. Concurrent expression of the cell‐cycle inhibitory protein p21 WAF1 also occurred. These data suggest that EP 3 receptors produce epidermal growth inhibition through the action of DAG and ceramide second messengers.