| 11032978 |
Emamghoreishi M, Li PP, Schlichter L, Parikh SV, Cooke R, Warsh JJ: Associated disturbances in calcium homeostasis and G protein-mediated cAMP signaling in bipolar I disorder. Biol Psychiatry. 2000 Oct 1;48(7):665-73.
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). |
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