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beta1-Adrenergic receptors activate two distinct signaling pathways in striatal neurons.

Authors: Meitzen, J  Luoma, JI  Stern, CM  Mermelstein, PG 
Citation: Meitzen J, etal., J Neurochem. 2011 Mar;116(6):984-95. doi: 10.1111/j.1471-4159.2010.07137.x. Epub 2011 Jan 19.
Pubmed: (View Article at PubMed) PMID:21143600
DOI: Full-text: DOI:10.1111/j.1471-4159.2010.07137.x

Monoamine action in the dorsal striatum and nucleus accumbens plays essential roles in striatal physiology. Although research often focuses on dopamine and its receptors, norepinephrine (NE) and adrenergic receptors are also crucial in regulating striatal function. While noradrenergic neurotransmission has been identified in the striatum, little is known regarding the signaling pathways activated by beta-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a novel signaling pathway by which activation of beta1-adrenergic receptors leads to the rapid phosphorylation of cAMP response element binding protein (CREB), a transcription-factor implicated as a molecular switch underlying long-term changes in brain function. NE-mediated CREB phosphorylation requires beta1-adrenergic receptor stimulation of a receptor tyrosine kinase, ultimately leading to the activation of a Ras/Raf/MEK/MAPK/MSK signaling pathway. Activation of beta1-adrenergic receptors also induces CRE-dependent transcription and increased c-fos expression. In addition, stimulation of beta1-adrenergic receptors produces cAMP production, but surprisingly, beta1-adrenergic receptor activation of adenylyl cyclase was not functionally linked to rapid CREB phosphorylation. These findings demonstrate that activation of beta1-adrenergic receptors on striatal neurons can stimulate two distinct signaling pathways. These adrenergic actions can produce long-term changes in gene expression, as well as rapidly modulate cellular physiology. By elucidating the mechanisms by which NE and beta1-adrenergic receptor activation affects striatal physiology, we provide the means to more fully understand the role of monoamines in modulating striatal function, specifically how NE and beta1-adrenergic receptors may affect striatal physiology.


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CRRD Object Information
CRRD ID: 8693686
Created: 2014-07-17
Species: All species
Last Modified: 2014-07-17
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.