Serine/Threonine Phosphatase Inhibitors Decrease Adrenergic Arylalkylamine N -Acetyltransferase Induction in the Rat Pineal Gland
Autor: | Rainer Spessert, Lutz Vollrath, Maria Rapp |
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Rok vydání: | 2001 |
Předmět: |
chemistry.chemical_classification
endocrine system medicine.medical_specialty Endocrine and Autonomic Systems Endocrinology Diabetes and Metabolism fungi Phosphatase Adrenergic Protein tyrosine phosphatase Okadaic acid Biology Molecular biology Serine Cellular and Molecular Neuroscience chemistry.chemical_compound Endocrinology Enzyme chemistry Internal medicine Arylalkylamine medicine Threonine |
Zdroj: | Journal of Neuroendocrinology. 13:581-587 |
ISSN: | 0953-8194 |
Popis: | Adrenergic regulation of the pineal enzyme serotonin N-acetyltransferase [arylalkylamine N-acetyltransferase (AA-NAT); EC 2.3.1.87] accounts for the circadian rhythm in melatonin formation. In the present study, the role of protein phosphatases in the adrenergic regulation of rat pineal AA-NAT was investigated using specific inhibitors. In cultured pineals, the serine/threonine phosphatase type 1 and type 2A inhibitors okadaic acid and calyculin A significantly decreased adrenergically or cAMP-induced AA-NAT activity, whereas the serine/threonine phosphatase type 2B inhibitor cypermethrin and tyrosine phosphatase inhibitor dephostatin were ineffective. Reverse transcriptase-polymerase chain reaction (RT-PCR) data indicate that okadaic acid exerts its effect on cAMP-dependent AA-NAT induction by downregulating the amount of AA-NAT transcript. The ‘third’ messengers, inducible cAMP early repressor (ICER) and Fos-related antigene-2 (Fra-2), are believed to play a negative role in pineal AA-NAT transcription. Okadaic acid increased the cAMP responsiveness of neither ICER mRNA nor Fra-2 mRNA. Therefore, the regulatory role of pineal serine/threonine phosphatases in adrenergically stimulated AA-NAT expression probably does not depend on ICER or Fra-2. |
Databáze: | OpenAIRE |
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