The mechanism of serotonin (5-HT)-induced vasoconstriction and intracellular Ca²⁺ ([Ca²⁺]i) mobilization is not completely elucidated. 5-HT-induced vasoconstriction partly involves Ca²⁺-independent activation of Rho kinase. However, the mechanism of Rho kinase activation by 5-HT is still unknown. We examined the mechanism of 5-HT-induced [Ca²⁺]i mobilization of rat aortic smooth muscle cells using microscopic fluorometry. We also investigated whether 5-HT-induced constriction in rat thoracic aortas is mediated by Rho kinase activation through Src, epidermal growth factor receptor (EGFR), and extracellular signal-regulated kinase (Erk).
5-HT induced a biphasic [Ca²⁺]i response, and the initial [Ca²⁺]i increase was attenuated by inositol triphosphate (IP₃) receptor blocker, and inhibitors of Src and phosphoinositide 3-kinase (PI3K), but not L-type Ca²⁺ channel blocker (LCBB). The second [Ca²⁺]i increase was attenuated by LCBB. Contractile response to 5-HT significantly attenuated by inhibitors of Rho kinase, Erk1/2, Src, and EGFR. These data suggest that 5-HT induces Ca²⁺ release from the endoplasmic reticulum via Src and PI3K, and subsequently extracellular Ca²⁺ influx via L-type Ca²⁺ channel, and 5-HT-induced constriction is mediated by Rho kinase activation via Src, EGFR, and Erk in rat thoracic aortas.