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166954 [2018/11/20 14:26] (current)
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 +====== cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes.======
 +
 +** Article date:** 1989/4/1
 +~~META:date created = 1989-04-01~~
 +
 +** PubMed ID: 166954 **
 +
 +** Journal name: Proceedings of the National Academy of Sciences of the United States of America (ISSN: 0027-8424) **
 +
 +** ABSTRACT **
 +
 +The effects of the cyclic nucleotide cAMP on gamma-aminobutyric acid-gated chloride channel function were investigated. The membrane-permeant cAMP analog N6,​O2'​-dibutyryladenosine 3',​5'​-cyclic monophosphate inhibited muscimol-induced 36Cl- uptake into rat cerebral cortical synaptoneurosomes in a concentration-dependent manner (IC50 = 1.3 mM). The inhibition was due to a decrease in the maximal effect of muscimol, with no change in potency. Similar effects were observed with 8-(4-chlorophenylthio)adenosine 3',​5'​-cyclic monophosphate,​ 8-bromoadenosine 3',​5'​-cyclic monophosphate,​ and the phosphodiesterase inhibitor isobutylmethylxanthine. The effect of endogenous cAMP accumulation on the gamma-aminobutyric acid-gated Cl- channel was studied with forskolin, an activator of adenylate cyclase. Under identical conditions, in the intact synaptoneurosomes,​ forskolin inhibited muscimol-induced 36Cl- uptake and generated cAMP with similar potencies (IC50 = 14.3 microM; EC50 = 6.2 microM, respectively). Surprisingly,​ 1,​9-dideoxyforskolin,​ which does not activate adenylate cyclase, also inhibited the muscimol response, suggesting that forskolin and its lipophilic derivatives may interact with the Cl- channel directly. Indeed, forskolin inhibition of muscimol-induced 36Cl- uptake was extremely rapid (within 5 sec), preceding the accumulation of sufficient levels of cAMP. After 5 min, a slower phase of inhibition was seen, similar to the time course for cAMP accumulation. The data suggest that gamma-aminobutyric acid (GABAA) receptor function in brain can be regulated by cAMP-dependent phosphorylation.
 +
 +===== ===== 
 +
 +Author List: Heuschneider G, Schwartz R D
 +
 +Publication Types: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
 +
 +Substances mentioned in the article: Chloride Channels; Chlorides; Membrane Proteins; Colforsin; Muscimol; gamma-Aminobutyric Acid; Bucladesine;​ Cyclic AMP; 1-Methyl-3-isobutylxanthine; ​
 +
 +Mesh terms: 1-Methyl-3-isobutylxanthine/​pharmacology;​ Animals; Brain/​physiology;​ Bucladesine/​pharmacology;​ Chloride Channels; Chlorides/​physiology;​ Colforsin/​pharmacology;​ Cyclic AMP/​physiology;​ In Vitro Techniques; Membrane Proteins/​physiology;​ Muscimol/​pharmacology;​ Rats; Synaptosomes;​ gamma-Aminobutyric Acid/​physiology; ​
 +
 +Citations: ​  - //​[[4394110]]//​
 +  - //​[[3027574]]//​
 +  - //​[[177461]]//​
 +  - //​[[6101906]]//​
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 +  - //​[[6433343]]//​
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 +  - //​[[4041822]]//​
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 +  - //​[[2416932]]//​
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 +  - //​[[3746390]]//​
 +  - //​[[2430167]]//​
 +  - //​[[166954]]//​
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 +{{tag> Chloride_Channels Bucladesine Cyclic_AMP Chlorides 1-Methyl-3-isobutylxanthine gamma-Aminobutyric_Acid Membrane_Proteins Muscimol Colforsin }}
 +
 +{{keywords>​ Chloride Channels, Bucladesine,​ Cyclic AMP, Chlorides, 1-Methyl-3-isobutylxanthine,​ gamma-Aminobutyric Acid, Membrane Proteins, Muscimol, Colforsin}}
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166954.txt ยท Last modified: 2018/11/20 14:26 (external edit)