Dual modulation by adenosine of ATP-activated channels through GTP-binding proteins in rat pheochromocytoma PC12 cells.
Effects of adenosine on inward current activated by extracellular ATP were examined in rat pheochromocytoma PC12 cells. Adenosine induced two types of modulation on the current activated by 30 microM ATP; a low concentration of adenosine (1 microM) inhibited the current whereas a high concentration (> 10 microM) enhanced the current. Neither the inhibition nor the enhancement was observed in cells pretreated with pertussis toxin (PTX), or in cells dialyzed with guanosine 5'-O-(2-thiotriphosphate) trilithium salt (GDP beta S). In contrast, dialysis with K-252a, a protein kinase inhibitor, abolished the inhibition, but not the enhancement. Adenosine induced similar inhibition and enhancement on ATP-evoked increase in intracellular free Ca2+ concentration. The results suggest that adenosine produces dual modulation on the ATP-activated channels through different mechanisms involving PTX-sensitive GTP-binding proteins.
Inoue
K
K
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Watano
T
T
Koizumi
S
S
Nakazawa
K
K
Burnstock
G
G
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects*; D016716:PC12 Cells; D037342:Pertussis Toxin; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007473:Ion Channels; D010566:Virulence Factors, Bordetella; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000241:Adenosine; D002118:Calcium