cAMP and forskolin decrease. gamma. -aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes

Journal Article · Sat Apr 01 00:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.8.2938· OSTI ID:5264541

Heuschneider, G; Schwartz, R D ^[1]

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1. Duke Univ. Medical Center, Durham, NC (USA)

The effects of the cyclic nucleotide cAMP on {gamma}-aminobutyric acid-gated chloride channel function were investigated. The membrane-permeant cAMP analog N{sup 6}, O{sup 2{prime}}-dibutyryladenosine 3{prime},5{prime}-cyclic monophosphate inhibited muscimol-induced {sup 36}Cl{sup {minus}} uptake into rat cerebral cortical synaptoneurosomes in a concentration-dependent manner. 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{prime},5{prime}-cyclic monophosphate, 8-bromoadenosine 3{prime},5{prime}-cyclic monophosphate, and the phosphodiesterase inhibitor isobutylmethylxanthine. The effect of endogenous cAMP accumulation on the {gamma}-aminobutyric acid-gated Cl{sup {minus}} channel was studied with forskolin, an activator of adenylate cyclase. Under identical conditions, in the intact synaptoneurosomes, forskolin inhibited muscimol-induced {sup 36}Cl{sup {minus}} uptake and generated cAMP with similar potencies. 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{sup {minus}} channel directly. The data suggest that {gamma}-aminobutyric acid (GABA{sub A}) receptor function in brain can be regulated by cAMP-dependent phosphorylation.

• OSTI ID: 5264541
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:8; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AMINOBUTYRIC ACID
UPTAKE
CHLORINE 36
MEMBRANE TRANSPORT
BIOCHEMICAL REACTION KINETICS
NEUROREGULATORS
BIOCHEMISTRY
AMP
ANIONS
DOSE-RESPONSE RELATIONSHIPS
NUCLEOTIDES
RECEPTORS
TIME DEPENDENCE
AMINO ACIDS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CHARGED PARTICLES
CHEMISTRY
CHLORINE ISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
IONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MEMBRANE PROTEINS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
YEARS LIVING RADIOISOTOPES
550201* - Biochemistry- Tracer Techniques