FIG. 11.

Putative model for DON-induced hormone secretion by the STC-1 EEC model. This study suggests that DON initiates [Ca²⁺]_i increase in STC-1 cells via CaSR-mediated pathway that involves the following serial events: (1) PLC-mediated activation of the IP3 receptor and mobilization of intracellular Ca²⁺ stores, (2) activation of the TRPM5 Na²⁺ channel and resultant L-type VSCC-facilitated extracellular Ca²⁺ entry, and (3) amplification of extracellular Ca²⁺ entry by TRPA1 activation. The resultant elevation of [Ca²⁺]_i drives exocytosis of CCK, GLP-1, and potentially other hormones. The data presented here suggest that DON hijacks these normal physiologic processes mediated by CaSR, thereby disrupting homeostasis and mediating hormone release. Further investigation is needed to ascertain if DON allosterically interacts with CaSR or if the toxin activates this GPCR by an alternative mechanism. The symbol ⊥ indicates targets of antagonists used in this study.