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Glucocorticoid block of protein kinase C signalling in mouse pituitary corticotroph AtT20 D16:16 cells
Author(s) -
Tian Lijun,
Philp Janet A. C.,
Shipston Michael J.
Publication year - 1999
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.1469-7793.1999.0757u.x
Subject(s) - protein kinase c , endocrinology , medicine , chelerythrine , staurosporine , phorbol , diacylglycerol kinase , corticotropic cell , glucocorticoid , chemistry , bisindolylmaleimide , anterior pituitary , biology , signal transduction , biochemistry , hormone
1 The regulation of large conductance calcium‐ and voltage‐activated potassium (BK) currents by activation of the protein kinase C (PKC) and glucocorticoid signalling pathways was investigated in AtT20 D16:16 clonal mouse anterior pituitary corticotroph cells. 2 Maximal activation of PKC using the phorbol esters, 4β‐phorbol 12‐myristate, 13‐acetate (PMA), phorbol 12, 13 dibutyrate (PDBu) and 12‐deoxyphorbol 13‐phenylacetate (dPPA) elicited a rapid, and sustained, inhibition of the outward steady‐state voltage‐ and calcium‐ dependent potassium current predominantly carried through BK channels. 3 The effect of PMA was blocked by the PKC inhibitors bisindolylmaleimide I (BIS; 100 nM) and chelerythrine chloride (CHE; 25 μM) and was not mimicked by the inactive phorbol ester analogue 4α‐PMA. 4 PMA had no significant effect on the 1 mM tetraethylammonium (TEA)‐insensitive outward current or pharmacologically isolated, high voltage‐activated calcium current. 5 PMA had no significant effect on steady‐state outward current in cells pre‐treated for 2 h with 1 μM of the glucocorticoid agonist dexamethasone. Dexamethasone had no significant effect on steady‐state outward current amplitude or sensitivity to 1 mM TEA and did not block PMA‐induced translocation of the phorbol ester‐sensitive PKC isoforms, PKCα and PKCε, to membrane fractions. 6 Taken together these data suggest that in AtT20 D16:16 corticotroph cells BK channels are important targets for PKC action and that glucocorticoids inhibit PKC signalling downstream of PKC activation.