著者

Tamiko Suzuki-Nishimura Masayoshi Baba Shiori Otani Arisa Yamamoto Yasushi Kodama

出版者

Japanese Pharmacological Society

雑誌

日本薬理学会年会要旨集 (ISSN:24354953)

巻号頁・発行日

pp.PO3-4-11, 2018 (Released:2020-09-10)

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The manic depression drug lithium carbonate has many mechanisms of action. As one of these mechanisms is the inhibition of amine release from the end of synapses, we examined the effects of lithium carbonate on the IgE-independent histamine release from rat peritoneal mast cells. In the presence of 0.3 mM CaCl2, at concentrations from 0.3 to 3.0 mM, lithium carbonate inhibited the histamine release induced by bradykinin (BK) (10 μM), substance P (SP) (10 μM) or compound 48/80 (48/80) (1 μg/mL). The histamine release induced by 1 μg/mL of 48/80 was inhibited by lithium carbonate, but that by 5 μg/ml of 48/80 was not. The IgE independent activator GlcNAc-specific Datura stramonium agglutinin (DSA) releases histamine from rat mast cells similar with 48/80, and lithium carbonate also inhibited the histamine release induced by DSA at 100 μg/mL. BK, SP and 48/80 are well-known activators against MRGPR. Mouse MrgprB2 and human MRGPRX2 on mast cells are possible targets of the pseudo-allergic drug reactions involving mast cell activation. Rat peritoneal mast cells have similar MRGPR calcium-dependent and calcium-independent pathways for mast cell activation. Inhibition of BK- or SP-induced histamine release by lithium carbonate did not recover after increasing the extracellular calcium concentration, suggesting that MRGPR in rat mast cells may be a calcium-independent, G-protein dependent receptor. The effects of lithium carbonate suggested that lithium carbonate inhibited downstream of the common signal transduction pathway, following MRGPR activation induced by BK, SP, 48/80 or DSA. The clinical dose of lithium carbonate is from 0.5 to 1 mM, and addiction occurs from 1.8 to 2.5 mM. The inhibitory effects of lithium carbonate on the IgE-independent histamine release were observed at both the clinical and addictive doses in humans, suggesting that lithium carbonate similarly inhibits both histamine release from mast cells and brain amine release from synapses.