Neuron
Volume 1, Issue 7, September 1988, Pages 585-591
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Article
Pre- and postsynaptic GABAB receptors in the hippocampus have different pharmacological properties

https://doi.org/10.1016/0896-6273(88)90108-0Get rights and content

Abstract

Pharmacological properties of pre- and postsynaptic GABAB receptors were compared in CA1 hippocampal pyramidal neurons in vitro. The postsynaptic effects mediated by GABAB receptors, i.e., the baclofen-induced hyperpolarization, the bicuculline-resistant GABA response, and the slow inhibitory postsynaptic potential elicited by CA1 afferent stimulation, are all blocked by pertussis toxin (which inactivates some G proteins). These events are also suppressed by stimulating protein kinase C by phorbol esters and blocked by the selective GABAB antagonist phaclofen. In contrast, the baclofen-induced presynaptic depression of the excitatory post-synaptic potential elicited by CA1 afferent stimulation is resistant to the action of pertussis toxin and is not antagonized by phaclofen. However, this presynaptic inhibition can be antagonized by phorbol esters. These results indicate that the pre- and postsynaptic effects mediated by GABAB receptors in hippocampus have distinctly different pharmacological properties and possibly a different coupling mechanism.

References (27)

  • L. Bequinot et al.

    Phorbol esters induce transient internalization without degradation of unoccupied epidermal growth factor receptors

  • N.G. Bowery

    Actions and Interactions of GABA and Benzodiazepines

    (1984)
  • N.G. Bowery et al.

    (-) Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor

    Nature

    (1980)
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    Present address: Laboratoire de Neurophysiologie Pharmacologique, INSERM U 161, 2 rue d'Alésia, 75014 Paris, France.

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