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Serine/threonine phosphatase inhibitors decrease adrenergic arylalkylamine n-acetyltransferase induction in the rat pineal gland.

R Spessert·M Rapp·L Vollrath
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Abstract

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.

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AnimalsArylamine N-AcetyltransferaseCyclic AMP Response Element ModulatorDNA-Binding ProteinsEnzyme InductionFos-Related Antigen-2Marine ToxinsOkadaic AcidOxazolesPhosphoprotein PhosphatasesPineal GlandRNA, MessengerRatsRats, Sprague-DawleyRepressor ProteinsTranscription FactorsJournal ArticleResearch Support, Non-U.S. Gov't

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R Spessert, M Rapp, L Vollrath. 2001. Serine/threonine phosphatase inhibitors decrease adrenergic arylalkylamine n-acetyltransferase induction in the rat pineal gland.. https://doi.org/10.1046/j.1365-2826.2001.00669.x

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