Abstract
Membranes prepared from rat brain regions were used to measure the receptor-coupled and/or guanine nucleotide-binding protein (G protein)-mediated hydrolysis of exogenous [3H]phosphatidylinositol ([3H]PI). Guanosine 5′-O-(3-thiotriphosphate) (GTPγS) and NaF (in the presence of AlCl3) caused concentration-dependent stimulations of [3H]PI hydrolysis, supporting the conclusion that G proteins mediating [3H]PI hydrolysis can be activated in this preparation. Neither of these responses was altered by in vitro incubation with 8 mM LiCl, but both were reduced in hippocampal, striatal, and cortical membranes from rats that had been treated with lithium for 4 weeks compared with controls. Two cholinergic agonists, carbachol and pilocarpine, induced no hydrolysis of [3H]PI unless GTPγS was also present, in which case each equally stimulated [3H]PI hydrolysis above that obtained with GTPγS alone. In the presence of GTPγS several excitatory amino acid agonists stimulated [3H]PI hydrolysis to an extent similar to that of carbachol. After chronic lithium treatment, [3H]PI hydrolysis stimulated by carbachol was significantly attenuated, but the response to quisqualate was unaffected. Therefore, lithium added in vitro does not have an effect on cholinergic receptor- or G protein-mediated [3H]PI hydrolysis, but each of these is reduced by chronic lithium treatment. Because exogenous [3H]PI was provided as the substrate, it is evident that the inhibitory effect of chronic lithium treatment cannot be due to substrate depletion. Impaired function of G proteins appears to be the most likely mechanism accounting for attenuated [3H]PI hydrolysis after chronic administration of lithium.
Original language | English (US) |
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Pages (from-to) | 2200-2206 |
Number of pages | 7 |
Journal | Journal of neurochemistry |
Volume | 58 |
Issue number | 6 |
DOIs | |
State | Published - Jun 1992 |
Externally published | Yes |
Keywords
- Cholinergic system
- Glutamate
- Guanine nucleotide-binding proteins
- Lithium
- Phosphatidylinositol
- Phosphoinositides
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience