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Dose pipecolic acid interact with the central GABA-ergic system?

R Bernasconi, R S Jones, H Bittiger

Journal of Neural Transmission

|January 1, 1986

Summary

L-pipecolic acid (L-PA) does not strongly interact with GABA-mediated transmission in the brain. Electrophysiological and neurochemical studies found only weak effects, challenging previous GABA-mimetic action suggestions.

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Area of Science:

Neuroscience
Pharmacology

Background:

Endogenous imino acid L-pipecolic acid (L-PA) has been suggested to possess GABA-mimetic properties.
Previous studies indicated a significant interaction between L-PA and GABAergic systems.

Purpose of the Study:

To rigorously evaluate the proposed GABA-mimetic action of L-pipecolic acid (L-PA).
To investigate the in vivo effects of L-PA on neuronal activity and GABAergic transmission.

Main Methods:

Electrophysiological recordings from rat cortical neurons.
Neurochemical assays to assess GABA levels and synthesis.
Receptor binding studies for GABA-benzodiazepine-chloride channel complex.
Anticonvulsant activity tests in mice.

Main Results:

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Electrophysiological studies revealed only a weak, bicuculline-sensitive depressant action of L-PA on cortical neurons, contrary to prior reports.
L-PA demonstrated no significant affinity for the GABA-A receptor complex but showed weak affinity for the GABA-B receptor site.
L-PA did not exhibit anticonvulsant activity and had minimal impact on brain GABA levels or synthesis.

Conclusions:

The findings do not support a strong in vivo interaction between L-PA and GABA-mediated inhibitory transmission.
Previous suggestions of a potent GABA-mimetic action of L-PA require re-evaluation based on these results.