Abstract
Corticotropin-releasing hormone (CRH) has been shown to exhibit various functions in hippocampus. In the present study, we examined the effect of CRH on the expression of serum/glucocorticoid-inducible protein kinase-1 (SGK-1), a novel protein kinase, in primary cultured hippocampal neurons. A dose-dependent increase in mRNA and protein levels of SGK-1 as well as frequency of SGK-1-positive neurons occurred upon exposure to CRH (1 pmol/l to 10 nmol/l). These effects can be reversed by the specific CRH-R1 antagonist antalarmin but not by the CRH-R2 antagonist astressin 2B. Blocking adenylate cyclase (AC) activity with SQ22536 and PKA with H89 completely prevented CRH-induced mRNA and protein expression of SGK-1. Blockage of PLC or PKC did not block CRH-induced SGK-1 expression. Our results suggest that CRH act on CRH-R1 to stimulate SGK-1 mRNA and protein expression in cultured hippocampal neurons via a mechanism that is involved in AC/PKA signaling pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Blotting, Western
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Cells, Cultured
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Corticotropin-Releasing Hormone / pharmacology*
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Cyclic AMP / biosynthesis
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Enzyme Inhibitors / pharmacology
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Fluorescent Antibody Technique
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Hippocampus / cytology
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Hippocampus / drug effects
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Hippocampus / enzymology*
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Immediate-Early Proteins / biosynthesis*
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Immediate-Early Proteins / genetics
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Neurons / drug effects
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Neurons / enzymology*
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Phospholipase C beta / antagonists & inhibitors
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Phospholipase C beta / biosynthesis
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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Protein Serine-Threonine Kinases / biosynthesis*
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Protein Serine-Threonine Kinases / genetics
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RNA / biosynthesis
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RNA / genetics
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Rats
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Rats, Sprague-Dawley
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Receptors, Corticotropin-Releasing Hormone / drug effects*
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Reverse Transcriptase Polymerase Chain Reaction
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Stimulation, Chemical
Substances
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Enzyme Inhibitors
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Immediate-Early Proteins
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RNA, Messenger
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Receptors, Corticotropin-Releasing Hormone
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CRF receptor type 1
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RNA
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Corticotropin-Releasing Hormone
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Cyclic AMP
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Protein Serine-Threonine Kinases
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serum-glucocorticoid regulated kinase
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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Phospholipase C beta