Abstract
GMP-PNP, a non-hydrolyzable analog of GTP binds tightly to G-protein in the presence of Mg2+, so that the binding is stable even after exhaustive washings. This property was exploited to prepare membrane samples of rat brain where G-protein GTP-binding sites were saturated with GMP-PNP. Experiments carried out with these membranes showed that GTP, GMP-PNP, GDP-S and GMP (1 mM) inhibit the sodium-independent [3H]glutamate binding by 30-40% [F(4,40) = 5.9; p < .001], whereas only GMP-PNP activates adenylate cyclase activity [F(6,42) = 3.56; p < .01]. The inhibition of sodium-independent [3H]glutamate binding occurred in the absence of Mg2+. These findings suggest that guanine nucleotides may inhibit glutamate binding and activate adenylate cyclase through distinct mechanisms by acting on different sites.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenylyl Cyclases / metabolism*
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Animals
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Brain / drug effects
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Brain / metabolism*
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Cell Membrane / metabolism
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GTP-Binding Proteins / metabolism
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Glutamic Acid / metabolism*
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Guanine Nucleotides / metabolism
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Guanine Nucleotides / pharmacology*
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Guanosine Diphosphate / analogs & derivatives
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Guanosine Diphosphate / pharmacology
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Guanosine Monophosphate / pharmacology
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Guanosine Triphosphate / metabolism
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Guanylyl Imidodiphosphate / metabolism
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Magnesium / pharmacology
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Male
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Rats
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Rats, Wistar
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Sodium / pharmacology
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Thionucleotides / pharmacology
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Tritium
Substances
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Guanine Nucleotides
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Thionucleotides
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Tritium
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Guanosine Diphosphate
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Guanylyl Imidodiphosphate
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Glutamic Acid
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guanosine 5'-O-(2-thiodiphosphate)
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Guanosine Monophosphate
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Guanosine Triphosphate
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Sodium
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GTP-Binding Proteins
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Adenylyl Cyclases
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Magnesium