Cysteine sulfinic acid-induced release of D-[3H]aspartate and [14C]GABA in hippocampus slices: the role of sodium channels and cAMP.
Cysteine sulfinic acid, a putative transmitter in the brain induces release of D-[3H]aspartate and [14C]GABA without the help of any general depolarizing agent. Tetrodotoxin partially blocks the release of D-[3H]aspartate and completely blocks the induced release of [14C]GABA. Withdrawal of Ca2+ from the medium does not affect the D-[3H]aspartate release, but increases the extent of inhibition by tetrodotoxin. In contrast, removal of Ca2+ increases the cysteine sulfinic acid-induced [14C]GABA release, which remains totally blocked by the toxin. Anemonia sulcata toxin type II, which slows down Na+ channel inactivation, acts in synergism with cysteine sulfinic acid to increase the rate of release of both of the labeled amino acids. Comparison of glutamate with cysteine sulfinic acid in the same experiments indicates a different action pattern of the two acidic amino acids. Forskolin plus isobutyl methyl xanthine, which are known to raise intracellular cyclic adenosine monophosphate (cyclic AMP) levels, caused little release of the labeled amino acids on their own, but strongly enhanced the cysteine sulfinic acid-induced release. The experiments conducted by double labeling with D-[3H]aspartate and [14C]GABA, revealed several characteristic differences between the glutamatergic and the GABAergic neurons. It is tentatively concluded that cysteine sulfinic acid brings about excitation of the glutamatergic as well as the GABAergic neurons, leading to opening of Na+ channels which play a role in the release of both systems. Cyclic AMP, presumably by initiating phosphorylation of a specific component, has a remarkable potentiating effect on the release.
Minc-Golomb
D
D
Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.
Eimerl
S
S
Schramm
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000493:pharmacokinetics*; D002118:Calcium / Q000502:physiology; D003064:Cnidarian Venoms / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology; D018377:Neurotransmitter Agents; D051381:Rats; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics*
D000596:Amino Acids; D003064:Cnidarian Venoms; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D015222:Sodium Channels; D005576:Colforsin; D001224:Aspartic Acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C028800:toxin II (Anemonia sulcata); D003545:Cysteine; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; C013461:cysteine sulfinic acid