Norepinephrine Induction of Mitogen-Activated Protein Kinase Phosphatase-1 Expression in Rat Pinealocytes: Distinct Roles of α- and β-Adrenergic Receptors

In this study, we investigated the mechanisms through which norepinephrine (NE) regulates MAPK phosphatase-1 (MKP-1) expression in rat pinealocytes. Stimulation with NE (a mixed α- and β-adrenergic agonist) caused a rapid increase in MKP-1 mRNA and protein that peaked around 1 h post stimulation, and the response was sustained for at least 4 h. Selective activation of β-adrenergic receptors with isoproterenol for 1 h caused a similar increase in MKP-1 mRNA and protein as observed with NE, but at 3 h, the isoproterenol response was much lower relative to NE. In contrast, selective activation of α-adrenergic receptors caused only small increases in MKP-1 mRNA and protein and appeared to function primarily in prolonging the β-adrenergic-stimulated responses. In NE-stimulated pinealocytes, blockade of β-adrenergic receptors caused a rapid reduction in MKP-1 mRNA, but it had a minimal effect on MKP-1 protein. In contrast, blockade of α-adrenergic receptors specifically reduced NE-induced MKP-1 protein but not ...

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