Regulation of K+ channel mRNA expression by stimulation of adenosine A(2a)-receptors in cultured rat microgliaKust, BM., Biber, K., Van Calker, D. & Gebicke-Haerter, PJ., 15-Jan-1999, In : Glia. 25, 2, p. 120-130 11 p.
Research output: Contribution to journal › Article › Academic › peer-review
Previous investigations suggest that the expression of K+ channels in cultured rat microglia is related to the activation status of these cells. Both, lipopolysaccharide (LPS) and agents that raise intracellular cyclic AMP have been shown to inhibit microglial proliferation. LPS also regulates the mRNA expression levels of K+ channels in cultured microglia, which led us to investigate possible regulatory interactions between K+ channels and adenosine A(2a)-receptors, which are coupled to the cAMP-signal transduction pathway. The selective adenosine A(2a)-receptor agonist CGS 21680 induced enhanced mRNA expression of both Kv1.3 and ROMK1, as well as an elevation of Kv1.3 protein. The selective adenosine A(2a)-receptor antagonist aminophenol (ZM 241385) and the nonselective antagonist 8-phenyltheophylline (8-PT) inhibited these effects. Elevations of cyclic AMP by use of dibutyryl cyclic AMP (dbcAMP), phosphodiesterase-inhibitor (RO 20-1724), forskolin, or cholera toxin (CTX), strongly enhanced Kv1.3-mRNA expression, but decreased ROMK1-mRNA levels. Results from experiments with actinomycin D suggest that K+ channel mRNA levels in cultured microglia were regulated by altered mRNA synthesis. Evidently, the CGS 21680-induced effects upon Kv1.3 were mediated via an increase in intracellular cyclic AMP, whereas ROMK1-mRNA expression appeared to be regulated by coupling of adenosine A(2a)-receptors to an alternative pathway, which involves activation of protein kinase C (PKC). It is concluded that the cychc AMP second messenger system in microglia is not only involved in regulation of K+ channel activity, but also in regulation of de novo K+ channel synthesis. GLIA. 25:120-130, 1999. (C) 1999 Wiley-Liss, Inc.
|Number of pages||11|
|Publication status||Published - 15-Jan-1999|
- Kv1.3, ROMK1, CGS 21680, cyclic AMP, signal transduction, PROTEIN-KINASE-C, PERIPHERAL-BLOOD LYMPHOCYTES, POTASSIUM CHANNEL, A(2A)-ADENOSINE RECEPTOR, XENOPUS OOCYTES, CELLS, PROLIFERATION, BRAIN, CDNA, ACTIVATION