Serotonin increases cytoplasmic Ca2+ concentration in PC12h cells: effect of tachykinin peptides.
We report here that serotonin (5-hydroxytriptamine, 5-HT) induces an increase in intracellular Ca2+ concentration ([Ca2+]i) in rat pheochromocytoma PC12h cells, a subclone of PC12 cells, which was detected by using Ca2+ sensitive indicator dye fura-2. The [Ca2+]i increase completely disappeared when extracellular Ca2+ was chelated with excess EGTA and potently suppressed in Na+-free buffer. Nifedipine, a voltage-dependent L-type calcium channel blocker, significantly blocked the 5-HT response. Addition of another 4 mM Ca2+ to the cell suspension attenuated the [Ca2+]i increase induced by 5-HT, whereas the nicotinic action was remarkably potentiated. Furthermore, metoclopramide, a 5-HT3 receptor antagonist, inhibited the 5-HT response in a dose dependent manner. These findings suggest that the 5-HT-induced [Ca2+]i increase involves the mediation of a voltage-dependent Ca2+ channel, evoked by membrane depolarization via the activation of cation channel-type receptors, 5-HT3 receptors. We also noted the inhibitory action of tachykinin peptides on the 5-HT response, suggesting that the cell line is useful to investigate these neuromodulatory actions in the nervous system.
Takenouchi
T
T
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan.
Munekata
E
E
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects; D020746:Calcium Channels, L-Type; D020013:Calcium Signaling / Q000187:drug effects*; D002999:Clone Cells; D003593:Cytoplasm / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D016257:Fura-2 / Q000032:analysis / Q000378:metabolism; D008787:Metoclopramide / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D016716:PC12 Cells; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D015320:Tachykinins / Q000494:pharmacology*
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D010455:Peptides; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D015320:Tachykinins; D012701:Serotonin; D004533:Egtazic Acid; D012964:Sodium; D009543:Nifedipine; D008787:Metoclopramide; D002118:Calcium; D016257:Fura-2