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

ABSTRACT: 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 ?-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a novel signaling pathway by which activation of ?1-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 ?1-adrenergic receptor stimulation of a receptor tyrosine kinase, ultimately leading to the activation of a Ras/Raf/MEK/MAPK/MSK signaling pathway. Activation of ?1-adrenergic receptors also induces CRE-dependent transcription and increased c-fos expression. In addition, stimulation of ?1-adrenergic receptors produces cAMP production, but surprisingly, ?1-adrenergic receptor activation of adenylyl cyclase was not functionally linked to rapid CREB phosphorylation. These findings demonstrate that activation of ?1-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 ?1-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 ?1-adrenergic receptors may affect striatal physiology.

SUBMITTER: Meitzen J

PROVIDER: S-EPMC3078043 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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β1-Adrenergic receptors activate two distinct signaling pathways in striatal neurons.

Meitzen John J Luoma Jessie I JI Stern Christopher M CM Mermelstein Paul G PG

Journal of neurochemistry 20110119 6

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 β-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a ...[more]

PMID: 21143600

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

Publications

β1-Adrenergic receptors activate two distinct signaling pathways in striatal neurons.

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