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Regulation of serine (Ser)-31 and Ser40 tyrosine hydroxylase phosphorylation during morphine withdrawal in the hypothalamic paraventricular nucleus and nucleus tractus solitarius-A2 cell group: role of ERK1/2.

Author	Cristina Núñez, M Luisa Laorden, M Victoria Milanés
Citation Information	Endocrinology, 148:5780-93 (2007)
Keywords	Animals, Blotting, Western, Gene Expression, Hypothalamus, Immunohistochemistry, Male, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Morphine, Paraventricular Hypothalamic Nucleus, Phosphorylation, Proto-Oncogene Proteins c-fos, Rats, Rats, Sprague-Dawley, Serine, Solitary Nucleus, Tyrosine 3-Monooxygenase
Related Products	AB5935
Pub Med ID	17823252

Our previous studies have shown that naloxone-induced morphine withdrawal increases the hypothalamic-pituitary-adrenocortical (HPA) axis activity, which is dependent on a hyperactivity of noradrenergic pathways [nucleus tractus solitarius (NTS) A(2)] innervating the hypothalamic paraventricular nucleus (PVN). Short-term regulation of catecholamine biosynthesis occurs through phosphorylation of tyrosine hydroxylase (TH), which enhances enzymatic activity. In the present study, the effect of morphine withdrawal on site-specific TH phosphorylation in the PVN and NTS-A(2) was determined by quantitative blot immunolabeling and immunohistochemistry using phosphorylation state-specific antibodies. We show that naloxone-induced morphine withdrawal phosphorylates TH at Serine (Ser)-31 but not Ser40 in PVN and NTS-A(2), which is associated with both an increase in total TH immunoreactivity in NTS-A(2) and an enhanced TH activity in the PVN. In addition, we demonstrated that TH neurons phosphorylated at Ser31 coexpress c-Fos in NTS-A(2). We then tested whether pharmacological inhibition of ERK activation by ERK kinase contributes to morphine withdrawal-induced phosphorylation of TH at Ser31. We show that the ability of morphine withdrawal to stimulate phosphorylation at this seryl residue is reduced by SL327, an inhibitor of ERK(1/2) activation. These results suggest that morphine withdrawal increases noradrenaline turnover in the PVN, at least in part, via ERK(1/2)-dependent phosphorylation of TH at Ser31.