title: Associated disturbances in calcium homeostasis and G protein-mediated cAMP signaling in bipolar I disorder.
abstract: BACKGROUND
  Evidence of extensive cross-talk between calcium (Ca(2+))- and cAMP-mediated signaling systems suggests that previously reported abnormalities in Ca(2+) homeostasis in bipolar I (BP-I) patients may be linked to disturbances in the function of G proteins that mediate cAMP signaling.
  
  
  METHODS
  To test this hypothesis, the beta-adrenergic agonist, isoproterenol, and the G protein activator, sodium fluoride (NaF), were used to stimulate cAMP production in B lymphoblasts from healthy and BP-I subjects phenotyped on basal intracellular calcium concentration ([Ca(2+)](B)). cAMP was measured by radioimmunoassay and [Ca(2+)](B) by ratiometric fluorometry with fura-2.
  
  
  RESULTS
  Isoproterenol- (10 microM) stimulated cAMP formation was lower in intact B lymphoblasts from BP-I patients with high [Ca(2+)](B) (>/= 2 SD above the mean concentration of healthy subjects) compared with patients having normal B lymphoblast [Ca(2+)](B) and with healthy subjects. Although basal and NaF-stimulated cAMP production was greater in B lymphoblast membranes from male BP-I patients with high versus normal [Ca(2+)](B), there were no differences in the percent stimulation. This suggests the differences in NaF response resulted from higher basal adenylyl cyclase activity.
  
  
  CONCLUSIONS
  These findings suggest that trait-dependent disturbances in processes regulating beta-adrenergic receptor sensitivity and G protein-mediated cAMP signaling occur in conjunction with altered Ca(2+) homeostasis in those BP-I patients with high B lymphoblast [Ca(2+)](B).
authors.affiliation: Section of Biochemical Psychiatry, Centre for Addiction and Mental Health, Clarke Site, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Emamghoreishi
authors.forename: P P
authors.initials: PP
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Schlichter
authors.forename: S V
authors.initials: SV
authors.lastname: Parikh
authors.forename: R
authors.initials: R
authors.lastname: Cooke
authors.forename: J J
authors.initials: JJ
authors.lastname: Warsh
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology; D001714:Bipolar Disorder / Q000503:physiopathology*; D002118:Calcium / Q000502:physiology*; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012969:Sodium Fluoride / Q000494:pharmacology
chemical_list: D012969:Sodium Fluoride; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D002118:Calcium