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Characterization of intracellular calcium mobilization induced by remimazolam, a newly approved intravenous anesthetic

Fig 6

Characterization of remimazolam-induced calcium elevation; possible involvement of the G-protein coupled receptors.

(A) Fifteen minutes-pretreatment with U-73122, a phospholipase C (PLC) inhibitor, at 5 μM significantly inhibited the 10 μM acetylcholine (ACh)-induced calcium elevation in SHSY-5Y cells (n = 9–10, *** p = 0.0004, compared to control, Mann Whitney test). Similarly, 15 minutes-pretreatment with U-73122 significantly affect 300 and 500 μM remimazolam-induced calcium elevation in SHSY-5Y cells (n = 9–10, ** p = 0.0044, compared to control, Mann Whitney test, and n = 7–12, * p = 0.018, compared to control, Mann Whitney test, respectively). The horizontal line in each box indicates the median, the box shows the interquartile range (IQR), and the whiskers represent 1.5 × IQR. (B) Fifteen minutes-pretreatment with U-73122 at 5 μM significantly inhibited the 10 μM histamine-induced calcium elevation in HUVECs (n = 6, ** p = 0.0022, compared to control, Mann Whitney test). Similarly, 15 minutes-pretreatment with U-73122 significantly affected 300 and 500 μM remimazolam-induced calcium elevation in HUVECs (n = 5, ** p = 0.0079, compared to control, Mann Whitney test, and n = 5–8, * p = 0.0295, compared to control, Mann Whitney test, respectively). The horizontal line in each box indicates the median, the box shows the interquartile range (IQR), and the whiskers represent 1.5 × IQR.

Fig 6

doi: https://doi.org/10.1371/journal.pone.0263395.g006