Regulation of 90-Kilodalton Ribosomal S6 Kinase Phosphorylation in the Rat Pineal Gland

• Published in: Endocrinology (Philadelphia) 2003-08, Vol.144 (8), p.3344-3350
• Main Authors: Ho, A. K, Mackova, M, Cho, C, Chik, C. L
• Format: Article
• Language: English
• Subjects: Acetic acid; Acetyltransferase; Adrenergic alpha-Agonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Adrenergic receptors; Animals; Arylamine N-Acetyltransferase - metabolism; Biological and medical sciences; Circadian Rhythm; Cyclic GMP; Cyclic GMP - pharmacology; Endocrine system; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Homeostasis; Ionomycin; Kinases; Light; Male; MAP kinase; MAP Kinase Kinase 1; MAP Kinase Kinase 2; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; N-Acetyltransferase; Norepinephrine; Norepinephrine - pharmacology; Phorbol 12-myristate 13-acetate; Phosphorylation; Pineal gland; Pineal Gland - drug effects; Pineal Gland - enzymology; Pineal Gland - radiation effects; Prazosin; Propranolol; Propranolol - pharmacology; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - antagonists & inhibitors; Rats; Rats, Sprague-Dawley; Receptors (physiology); Receptors, Adrenergic, alpha-1 - physiology; Receptors, Adrenergic, beta - physiology; Ribosomal protein S6 kinase; Ribosomal Protein S6 Kinases, 90-kDa - analysis; Ribosomal Protein S6 Kinases, 90-kDa - metabolism; Signal Transduction
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2003-0215

In this study we investigated diurnal changes in the activation state of the 90-kDa ribosomal S6 kinase (p90RSK) in the rat pineal gland. In animals housed under a lighting regimen with 12 h of light, we found an increase in phosphorylated p90RSK during the dark phase, and this increase was abolished by treatment with propranolol or continuous exposure to light. To determine the intracellular mechanism involved, rat pinealocytes were treated with norepinephrine. Norepinephrine caused a parallel increase in phosphorylated p42/44 MAPK (p42/44MAPK) and p90RSK that was reduced by prazosin or propranolol, indicating involvement of both α1- and β-adrenergic receptors. Treatment with dibutyryl cGMP, 4β-phorbol 12-myristate 13-acetate, or ionomycin mimicked norepinephrine-stimulated p90RSK phosphorylation, whereas dibutyryl cAMP caused a decrease in p90RSK phosphorylation. Inhibition of p42/44MAPK activation by UO126 was effective in reducing norepinephrine-stimulated p90RSK phosphorylation. Moreover, UO126 had an inhibitory effect on norepinephrine-stimulated arylalkyl-N-acetyltransferase activity. These results indicate that the adrenergically regulated nocturnal increase in p90RSK phosphorylation is mainly mediated through a cGMP→p42/44MAPK-dependent mechanism.