title: Effect of desipramine on inositol phosphate formation and inositol phospholipids in rat brain and human platelets.
abstract: To examine the mechanism of action of antidepressant drugs, we studied the effect of desipramine (DMI) in vitro on agonist-stimulated inositol phosphate formation and inositol phospholipids in rat brain and human platelets. We observed that DMI inhibited thrombin-stimulated 3H-inositol bisphosphate (IP2) and 3H-inositol trisphosphate (IP3) but not 3H-inositol monophosphate (IP1) formation in human platelets. DMI also inhibited norepinephrine (NE) and serotonin (5-HT) stimulated 3H-IP1 formation in rat cerebral cortex. DMI increased levels of all three 3H-inositol phospholipids, 3H-phosphatidyl inositol (PI), 3H-PI-4-phosphate (PIP), and 3H-PI 4,5-bisphosphate (PIP2), in both platelets and rat cortex. The decreased formation of inositol phosphates and increased levels of [3H]-PI, [3H]-PIP, and [3H]-PIP2 by DMI appears to be due to the inhibition of the enzyme phospholipase C rather than its effects on receptors. It is thus possible that interaction of tricyclic antidepressant drugs with the PI-signaling system may be related to their mechanism of action.
authors.affiliation: Illinois State Psychiatric Institute, Chicago 60612.
authors.forename: G N
authors.initials: GN
authors.lastname: Pandey
authors.forename: S C
authors.initials: SC
authors.lastname: Pandey
authors.forename: J M
authors.initials: JM
authors.lastname: Davis
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis*; D010743:Phospholipids / Q000096:biosynthesis*; D051381:Rats
chemical_list: D007295:Inositol Phosphates; D010743:Phospholipids; D003891:Desipramine