Potentiation by cadmium ion of ATP-evoked dopamine release in rat phaeochromocytoma cells.
1. The effects of cadmium ion (Cd2+) on release of dopamine and on an inward current evoked by extracellular ATP were investigated in rat phaeochromocytoma PC12 cells. 2. Cd2+ (100 microM-3 mM) potentiated the dopamine release evoked by 30 microM ATP from the cells. Cd2+ (100 microM) shifted the concentration-response curve of ATP-evoked dopamine release to the left without affecting the maximal response. 3. Suramin (30 microM) completely abolished the dopamine release evoked by 30 microM ATP but only partially inhibited the release evoked by 100 microM ATP consistent with its role as a competitive antagonist. The response evoked by 30 microM ATP in the presence of Cd2+ (300 microM) was comparable to that observed with 100 microM ATP alone; however, only the former was almost completely inhibited by suramin. 4. Cd2+ (100 microM) potentiated an inward current activated by 30 microM ATP alone. A higher concentration of Cd2+ (300 microM) had a smaller effect on amplitude potentiation but significantly prolonged the duration of the current. 5. The time-course of the ATP-evoked dopamine release was investigated using a real-time monitoring system for dopamine release. Although Cd2+ (300 microM) had little effect on the time-course of activation the ATP-evoked dopamine release, it produced a long-lasting dopamine release which slowly returned to the baseline. 6. Taken together, these observations suggest that Cd2+ enhances ATP-evoked dopamine release by affecting P2-purinoceptor/channels. The enhancement may be attributed to a Cd(2+)-dependent increase in sensitivity to ATP.
Ikeda
M
M
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Koizumi
S
S
Nakazawa
K
K
Inoue
K
K
Ito
K
K
Inoue
K
K
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D019256:Cadmium Chloride / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D013498:Suramin / Q000494:pharmacology
D018048:Receptors, Purinergic P2; D013498:Suramin; D000255:Adenosine Triphosphate; D019256:Cadmium Chloride; D004298:Dopamine