Associated disturbances in calcium homeostasis and G protein–mediated cAMP signaling in bipolar I disorder

Autor: Robert G. Cooke, Sagar V. Parikh, Lyanne C. Schlichter, Masoumeh Emamghoreishi, Jerry J. Warsh, Peter P. Li
Rok vydání: 2000
Předmět:
Zdroj: Biological Psychiatry. 48:665-673
ISSN: 0006-3223
DOI: 10.1016/s0006-3223(00)00884-2
Popis: 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 β-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 μM) 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 β-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 .
Databáze: OpenAIRE
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