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Inhibition of Voltage‐Sensitive Calcium Channels by the A 2A Adenosine Receptor in PC12 cells
Author(s) -
Park TaeJu,
Chung Sungkwon,
Han Myung Kwan,
Kim UhHyun,
Kim KyongTai
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71031251.x
Subject(s) - adenosine , agonist , adenosine receptor , inhibitory postsynaptic potential , medicine , receptor , endocrinology , biology , chemistry , biochemistry
The role of the A 2A adenosine receptor in regulating voltage‐sensitive calcium channels (VSCCs) was investigated in PC12 cells. Ca 2+ influx induced by membrane depolarization with 70 m M K + could be inhibited with CGS21680, an A 2A receptor‐specific agonist. Both L‐ and N‐type VSCCs were inhibited by CGS21680 treatment. Effects of adenosine receptor agonists and antagonists indicate that the typical A 2A receptor mediates inhibition of VSCCs. Cholera toxin (CTX) treatment for 24 h completely eliminated the CGS21680 potency. Similar inhibitory effects on VSCCs were obtained by membrane‐permeable activators of protein kinase A (PKA). These effects were blocked by Rp ‐adenosine‐3′,5′‐cyclic monophosphothioate, a PKA inhibitor. The data suggest that activation of the A 2A receptor leads to inhibition of VSCCs via a CTX‐sensitive G protein and PKA. ATP pretreatment caused a reduction in subsequent rise in cytosolic free Ca 2+ concentration induced by 70 m M K + , presumably by inactivation of VSCCs. Simultaneous treatment with ATP and CGS21680 produced significantly greater inhibition of VSCCs than treatment with CGS21680 or ATP alone. Furthermore, the CGS21680‐induced inhibition of VSCCs was not affected by the presence of reactive blue 2. CGS21680 still significantly inhibited ATP‐evoked Ca 2+ influx without VSCC activity after cobalt or 70 m M K + pretreatment. These data suggest that the A 2A receptor‐sensitive VSCCs differ from those activated by ATP treatment. Although A 2A receptors induce inhibition of VSCCs as well as ATP‐induced Ca 2+ influx, the two inhibitory effects are clearly distinct from each other.