title: Lithium modulation of second messenger signal amplification in man: inhibition of phosphatidylinositol-specific phospholipase C and adenylate cyclase activity.
abstract: The activity of phosphatidylinositol-specific phospholipase C was significantly reduced in platelets obtained from 20 euthymic manic-depressive patients on therapeutic lithium doses (mean blood level 0.85 mEq/l) compared to an age- and sex-matched group of 36 control subjects. The activities of prostaglandin E1-, aluminum/NaF-, and forskolin-stimulated platelet adenylate cyclase activity were also measured in a similar group of 16 lithium-treated and 22 control subjects. A marked reduction in both postreceptor (aluminum/NaF and forskolin) and receptor-stimulated (prostaglandin E1) platelet adenylate cyclase activity was observed in the lithium-treated group (mean blood level 0.81 mEq/l). These findings support the hypothesis that lithium's therapeutic mode of action in manic-depressive psychosis is mediated by the combined down-regulation of both principal second messenger systems, inositol phosphates and cyclic adenosine monophosphate, by reducing the activity of phosphatidylinositol-specific phospholipase C and adenylate cyclase.
authors.affiliation: Department of Research, Nashim Hospital, Jerusalem, Israel.
authors.forename: R P
authors.initials: RP
authors.lastname: Ebstein
authors.forename: B
authors.initials: B
authors.lastname: Lerer
authors.forename: E R
authors.initials: ER
authors.lastname: Bennett
authors.forename: B
authors.initials: B
authors.lastname: Shapira
authors.forename: S
authors.initials: S
authors.lastname: Kindler
authors.forename: Z
authors.initials: Z
authors.lastname: Shemesh
authors.forename: N
authors.initials: N
authors.lastname: Gerstenhaber
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000201:enzymology; D001792:Blood Platelets / Q000187:drug effects; D005260:Female; D006801:Humans; D008094:Lithium / Q000627:therapeutic use*; D016651:Lithium Carbonate; D008297:Male; D008875:Middle Aged; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010726:Phosphodiesterase Inhibitors; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D010726:Phosphodiesterase Inhibitors; D016651:Lithium Carbonate; D008094:Lithium; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase