Presynaptic GABAA receptors in vertebrate synapses.

Abstract

The presynaptic gamma-aminobutyric acidA (GABAA) receptor has long been considered as the site for 'presynaptic inhibition' of synaptic transmission in the central nervous system (CNS). However, recent reports have indicated that the activation of GABAA receptors depolarizes primary afferent neurons and actually facilitates the release of GABAA, noradrenaline, adenosine, and luteinizing hormone (LH) in central and peripheral tissues. Isoguvacine, a GABAA receptor agonist, enhances substance P (SP) release in the spinal cord. GABAB receptor agonists, bu not GABAA receptor agonists, produce behavioral antinociception in the spinal cord. Baclofen does not directly depolarize the postsynaptic membrane, but presynaptically inhibits the activity of dorsal horn neurons. The excitatory postsynaptic potential (EPSP) evoked by stimulation of dorsal root C-fibers is inhibited by baclofen. Baclofen and GABA inhibit SP release from the primary afferent terminals by activating GABAB receptors. The activation of GABAB receptors inhibits calcium currents in neurons of dorsal roots ganglia (DRG). It is likely that the GABAA receptors act as a site for 'presynaptic facilitation' of transmitter release in the CNS.