Activation of phosphodiesterase IV during desensitization of the A(2A) adenosine receptor-mediated cyclic AMP response in rat pheochromocytoma (PC12) cells

Yu Hsin Chang, Marco Conti, Yi Chao Lee, Hsing Lin Lai, Yung Hao Ching, Yijuang Chern

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Prolonged activation of an A(2A) adenosine receptor significantly inhibits the cellular response to subsequent stimulation (A(2A) desensitization). We have reported previously that activation of phosphodiesterase (PDE) contributes to A(2A) desensitization in PC12 cells. In the present study, we show that a type IV PDE (PDE4)-selective inhibitor (Ro 20-1724) effectively blocks the increase in PDE activity in desensitized cells. Thus, PDE4 appears to be the PDE specifically activated during A(2A) desensitization in PC12 cells. Prolonged treatment of PC12 cells with an A(2A)-selective agonist (CGS21680) leads to increased PDE4 activity in a dose-dependent manner, which can be blocked by an A(2A)-selective antagonist [8-(3-chlorostyryl)caffeine]. Using two PDE4 antibodies, we were able to demonstrate that the levels of two PDE4-immunoreactive bands (72 and 79 kDa) were increased significantly during A(2A) desensitization. Prolonged treatment with forskolin to elevate intracellular cyclic AMP contents also resulted in increased PDE4 activity. In addition, activation of PDE4 activity during A(2A) desensitization could be blocked by a protein kinase A (PKA)- selective inhibitor (H89) and was not observed in a PKA-deficient PC12 cell line (A123). Taken together, activation of PDE4 via a cyclic AMP/PKA- dependent pathway plays a critical role in dampening the signal of the A(2A) receptor.

Original languageEnglish
Pages (from-to)1300-1309
Number of pages10
JournalJournal of Neurochemistry
Volume69
Issue number3
Publication statusPublished - Sep 1997
Externally publishedYes

Fingerprint

Type 4 Cyclic Nucleotide Phosphodiesterase
Adenosine A2A Receptors
PC12 Cells
Pheochromocytoma
Cyclic AMP
Rats
Phosphoric Diester Hydrolases
Cyclic AMP-Dependent Protein Kinases
Chemical activation
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
Phosphodiesterase 4 Inhibitors
Adenylate Kinase
Colforsin
Cells
Cell Line
Antibodies

Keywords

  • Adenosine
  • Cyclic AMP
  • Desensitization
  • Phosphodiesterase IV
  • Protein kinase A
  • Receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Activation of phosphodiesterase IV during desensitization of the A(2A) adenosine receptor-mediated cyclic AMP response in rat pheochromocytoma (PC12) cells. / Chang, Yu Hsin; Conti, Marco; Lee, Yi Chao; Lai, Hsing Lin; Ching, Yung Hao; Chern, Yijuang.

In: Journal of Neurochemistry, Vol. 69, No. 3, 09.1997, p. 1300-1309.

Research output: Contribution to journalArticle

Chang, Yu Hsin ; Conti, Marco ; Lee, Yi Chao ; Lai, Hsing Lin ; Ching, Yung Hao ; Chern, Yijuang. / Activation of phosphodiesterase IV during desensitization of the A(2A) adenosine receptor-mediated cyclic AMP response in rat pheochromocytoma (PC12) cells. In: Journal of Neurochemistry. 1997 ; Vol. 69, No. 3. pp. 1300-1309.
@article{f587064431f54993a0cd5909369ff915,
title = "Activation of phosphodiesterase IV during desensitization of the A(2A) adenosine receptor-mediated cyclic AMP response in rat pheochromocytoma (PC12) cells",
abstract = "Prolonged activation of an A(2A) adenosine receptor significantly inhibits the cellular response to subsequent stimulation (A(2A) desensitization). We have reported previously that activation of phosphodiesterase (PDE) contributes to A(2A) desensitization in PC12 cells. In the present study, we show that a type IV PDE (PDE4)-selective inhibitor (Ro 20-1724) effectively blocks the increase in PDE activity in desensitized cells. Thus, PDE4 appears to be the PDE specifically activated during A(2A) desensitization in PC12 cells. Prolonged treatment of PC12 cells with an A(2A)-selective agonist (CGS21680) leads to increased PDE4 activity in a dose-dependent manner, which can be blocked by an A(2A)-selective antagonist [8-(3-chlorostyryl)caffeine]. Using two PDE4 antibodies, we were able to demonstrate that the levels of two PDE4-immunoreactive bands (72 and 79 kDa) were increased significantly during A(2A) desensitization. Prolonged treatment with forskolin to elevate intracellular cyclic AMP contents also resulted in increased PDE4 activity. In addition, activation of PDE4 activity during A(2A) desensitization could be blocked by a protein kinase A (PKA)- selective inhibitor (H89) and was not observed in a PKA-deficient PC12 cell line (A123). Taken together, activation of PDE4 via a cyclic AMP/PKA- dependent pathway plays a critical role in dampening the signal of the A(2A) receptor.",
keywords = "Adenosine, Cyclic AMP, Desensitization, Phosphodiesterase IV, Protein kinase A, Receptor",
author = "Chang, {Yu Hsin} and Marco Conti and Lee, {Yi Chao} and Lai, {Hsing Lin} and Ching, {Yung Hao} and Yijuang Chern",
year = "1997",
month = "9",
language = "English",
volume = "69",
pages = "1300--1309",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Activation of phosphodiesterase IV during desensitization of the A(2A) adenosine receptor-mediated cyclic AMP response in rat pheochromocytoma (PC12) cells

AU - Chang, Yu Hsin

AU - Conti, Marco

AU - Lee, Yi Chao

AU - Lai, Hsing Lin

AU - Ching, Yung Hao

AU - Chern, Yijuang

PY - 1997/9

Y1 - 1997/9

N2 - Prolonged activation of an A(2A) adenosine receptor significantly inhibits the cellular response to subsequent stimulation (A(2A) desensitization). We have reported previously that activation of phosphodiesterase (PDE) contributes to A(2A) desensitization in PC12 cells. In the present study, we show that a type IV PDE (PDE4)-selective inhibitor (Ro 20-1724) effectively blocks the increase in PDE activity in desensitized cells. Thus, PDE4 appears to be the PDE specifically activated during A(2A) desensitization in PC12 cells. Prolonged treatment of PC12 cells with an A(2A)-selective agonist (CGS21680) leads to increased PDE4 activity in a dose-dependent manner, which can be blocked by an A(2A)-selective antagonist [8-(3-chlorostyryl)caffeine]. Using two PDE4 antibodies, we were able to demonstrate that the levels of two PDE4-immunoreactive bands (72 and 79 kDa) were increased significantly during A(2A) desensitization. Prolonged treatment with forskolin to elevate intracellular cyclic AMP contents also resulted in increased PDE4 activity. In addition, activation of PDE4 activity during A(2A) desensitization could be blocked by a protein kinase A (PKA)- selective inhibitor (H89) and was not observed in a PKA-deficient PC12 cell line (A123). Taken together, activation of PDE4 via a cyclic AMP/PKA- dependent pathway plays a critical role in dampening the signal of the A(2A) receptor.

AB - Prolonged activation of an A(2A) adenosine receptor significantly inhibits the cellular response to subsequent stimulation (A(2A) desensitization). We have reported previously that activation of phosphodiesterase (PDE) contributes to A(2A) desensitization in PC12 cells. In the present study, we show that a type IV PDE (PDE4)-selective inhibitor (Ro 20-1724) effectively blocks the increase in PDE activity in desensitized cells. Thus, PDE4 appears to be the PDE specifically activated during A(2A) desensitization in PC12 cells. Prolonged treatment of PC12 cells with an A(2A)-selective agonist (CGS21680) leads to increased PDE4 activity in a dose-dependent manner, which can be blocked by an A(2A)-selective antagonist [8-(3-chlorostyryl)caffeine]. Using two PDE4 antibodies, we were able to demonstrate that the levels of two PDE4-immunoreactive bands (72 and 79 kDa) were increased significantly during A(2A) desensitization. Prolonged treatment with forskolin to elevate intracellular cyclic AMP contents also resulted in increased PDE4 activity. In addition, activation of PDE4 activity during A(2A) desensitization could be blocked by a protein kinase A (PKA)- selective inhibitor (H89) and was not observed in a PKA-deficient PC12 cell line (A123). Taken together, activation of PDE4 via a cyclic AMP/PKA- dependent pathway plays a critical role in dampening the signal of the A(2A) receptor.

KW - Adenosine

KW - Cyclic AMP

KW - Desensitization

KW - Phosphodiesterase IV

KW - Protein kinase A

KW - Receptor

UR - http://www.scopus.com/inward/record.url?scp=0030878075&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030878075&partnerID=8YFLogxK

M3 - Article

VL - 69

SP - 1300

EP - 1309

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 3

ER -