Etomidate inhibits [3H]noradrenaline release from SH-SY5Y human neuroblastoma cells.
We have examined the effects of the intravenous anaesthetic induction agent etomidate on K+ and carbachol evoked [3H]noradrenaline ([3H]NA) release and the associated increase in [Ca2+]i in SH-SY5Y human neuroblastoma cells in a attempt to study potential anaesthetic target site(s). Preincubation with etomidate produced a dose-dependent inhibition of both K+ and carbachol evoked [3H]NA release with estimated IC50 values of 88 and 69 microM, respectively. Only K+ stimulated increase in [Ca2+]i was inhibited by etomidate preincubation with an IC50 of 146 microM. Acute addition of etomidate after K+ challenge also inhibited the increase in [Ca2+]i with an IC50 of 99 microM. In addition etomidate displaced the binding of [3H]PN200-110 to L-type voltage sensitive Ca2+ channels with a Ki of 48 microM. As K+ but not carbachol evoked [3H]NA release is extracellular Ca2+ dependent and was inhibited by etomidate these data coupled with the PN200-110 displacement studies suggest that etomidate may interact with L-type voltage sensitive Ca2+ channels. The inhibition of carbachol evoked release without affecting the associated increase in [Ca2+]i suggests that etomidate may exert additional effects at either the muscarinic receptor or the secretory machinery in these cells.
Sikand
K S
KS
University Department of Anaesthesia, Leicester Royal Infirmary, UK.
Hirota
K
K
Smith
G
G
Lambert
D G
DG
D002118:Calcium / Q000032:analysis; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005045:Etomidate / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000737:chemistry / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002217:Carbachol; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D005045:Etomidate