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In Vivo Evidence that Lithium Inactivates G i Modulation of Adenylate Cyclase in Brain
Author(s) -
Masana Monica I.,
Bitran Jose A.,
Hsiao John K.,
Potter William Z.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb08891.x
Subject(s) - cholera toxin , adenylate cyclase toxin , adenylate kinase , pertussis toxin , forskolin , cyclase , medicine , endocrinology , adp ribosylation , chemistry , in vivo , lithium (medication) , g protein , stimulation , biology , biochemistry , receptor , nad+ kinase , enzyme , microbiology and biotechnology
In vivo microdialysis of cyclic AMP from prefron‐tal cortex complemented by ex vivo measures was used to investigate the possibility that lithium produces functional changes in G proteins that could account for its effects on adenylate cyclase activity. Four weeks of lithium administration (serum lithium concentration of 0.85 ±0.05 m M ; n = 11) significantly increased the basal cyclic AMP content in dialysate from prefrontal cortex of anesthetized rats. Forskolin infused through the probe increased dialysate cyclic AMP, but the magnitude of this increase was unaffected by chronic lithium administration. Inactivation of the inhibitory guanine nucleotide binding protein G i with pertussis toxin increased dialysate cyclic AMP in control rats, as did stimulation with cholera toxin (which activates the stimulatory guanine nucleotide binding protein G s ). The effect of pertussis toxin was abolished following chronic lithium, whereas the increase in cyclic AMP after cholera toxin was enhanced. In vitro pertussis toxin‐catalyzed ADP ribosyla‐tion of α i (and α o ) was increased by 20% in prefrontal cortex from lithium‐treated rats, but the α i and α s contents (as determined by immunoblot) as well as the cholera toxin‐catalyzed ADP ribosylation of α s were unchanged. Taken together, these results suggest that chronic lithium administration may interfere with the dissociation of G i into its active components and thereby remove a tonic inhibitory influence on adenylate cyclase, with resultant enhanced basal and cholera toxin‐stimulated adenylate cyclase activity.