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篇名 Regulation of Adenylyl Cyclase Type VI Activity During Desensitization of the A2a Adenosine Receptor-Mediated Cyclic AMP Response: Role for Protein Phosphatase 2A
卷期 13
作者 YIJUANG CHERN 、 JIN-YI CHIOU 、 HSING-LIN LAI 、 MING-HSIEN TSAI
頁次 047-054
關鍵字 TSCI
出刊日期 199509

中文摘要

英文摘要

We reported earlier that inhibition of adenylyl cyclase activity is a mechanism involved in desensitization of the A2a adenosine receptor-mediated cAMP response (A2a desensitization) in rat pheochromocytoma PC-12 cells. Here, we investigated the molecular mechanism that modulates adenylyl cyclase activity during A2a desensitization. Reversible inhibition of forskolin-evoked adenylyl cyclase activity in desensitized cells occurred after incubation with an A2a-selective adenosine agonist (CGS21680). However, when okadaic acid (a relatively protein phosphatase 2A-specific phosphatase inhibitor) was added after agonist removal, adenylyl cyclase activity did not recover. Okadaic acid caused significant dose-dependent inhibition of adenylyl cyclase activity in intact PC-12 cells. Prolonged exposure of okadaic acid-treated PC-12 cells to adenosine agonists did not evoke further inhibition, suggesting that the inhibition of adenylyl cyclase activity during A2a desensitization may operate through a pathway that overlaps with the increased phos- phorylation caused by okadaic acid.

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