Inhibition of voltage-sensitive calcium channels by the A2A adenosine receptor in PC12 cells.
The role of the A2A adenosine receptor in regulating voltage-sensitive calcium channels (VSCCs) was investigated in PC12 cells. Ca2+ influx induced by membrane depolarization with 70 mM K+ could be inhibited with CGS21680, an A2A 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 A2A 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 A2A 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 Ca2+ concentration induced by 70 mM 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 Ca2+ influx without VSCC activity after cobalt or 70 mM K+ pretreatment. These data suggest that the A2A receptor-sensitive VSCCs differ from those activated by ATP treatment. Although A2A receptors induce inhibition of VSCCs as well as ATP-induced Ca2+ influx, the two inhibitory effects are clearly distinct from each other.
Park
T J
TJ
Department of Life Science, Pohang University of Science and Technology (POSTECH), Hyoja Dong, Republic of Korea.
Chung
S
S
Han
M K
MK
Kim
U H
UH
Kim
K T
KT
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002772:Cholera Toxin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010627:Phenethylamines; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D002772:Cholera Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D000241:Adenosine