Phenylethylamine induces an increase in cytosolic ca²⁺ in Yeast

β-Phenylethylamine (PEA) induced an increase in cytosolic free calcium ion concentration ([Ca²⁺]_c) in Saccharomyces cereviseae cells monitored with transgenic aequorin, a Ca²⁺-dependent photoprotein. The PEA-induced [Ca²⁺]_c increase was dependent on the concentrations of PEA applied, and the Ca²⁺ mostly originated from an extracellular source. Preceding the Ca²⁺ influx, H₂O₂ was generated in the cells by the addition of PEA. Externally added H₂O₂ also induced a [Ca²⁺]_c increase. These results suggest that PEA induces the [Ca²⁺]_c increase via H₂O₂ generation. The PEA-induced [Ca²⁺]_c increase occurred in the mid1 mutant with a slightly smaller peak than in the wild-type strain, indicating that Mid1, a stretch-activated nonselective cation channel, may not be mainly involved in the PEA-induced Ca²⁺ influx. When PEA was applied, the MATa mid1 mutant was rescued from α-factor-induced death in a Ca²⁺-limited medium, suggesting that the PEA-induced [Ca²⁺]_c increase can reinforce calcium signaling in the mating pheromone response pathway.