Triethyltin interferes with Ca2+ signaling and potentiates norepinephrine release in PC12 cells.

We have investigated the effects of triethyltin (TET) on agonist-stimulated Ca2+ signaling and neurosecretion in PC12 cells. Treatment of PC12 cells with 10 microM TET elicited a slow increase of the resting cytosolic free Ca2+ concentration due to Ca2+ release from intracellular stores. Furthermore, TET modified the Ca2+ responses elicited by bradykinin (Bk), adenosine triphosphate (ATP), or high K+. TET potentiated the peak Ca2+ response stimulated by Bk in both the presence and the absence of extracellular Ca2+, and prolonged the recovery phase after ATP stimulation. In contrast, the Ca2+ transient elicited by bathing cells in high K+ was markedly reduced, suggesting that TET can differentially affect several targets on Ca2+-signaling pathways. Neurotransmitter depletion follows in vivo exposure to TET. Since neurotransmitter secretion is strictly dependent on intracellular Ca2+ signals we also investigated whether treatment with TET modified norepinephrine release from PC12 cells. TET did not elicit norepinephrine release, but it enhanced the release of norepinephrine induced by Bk or ATP. The increased release of norepinephrine elicited in combination with Bk was independent from extracellular Ca2+. Our results suggest that possible neurotoxic effects of TET can derive from its ability to modulate Ca2+ signaling and eventually neurosecretion.