GABAB Receptor-Mediated Inhibition of Synaptic Transmission in the Hippocampus: Pharmacology and Intracellular Mechanisms
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system that affects cellular excitability by opening or closing a variety of ion channels or by modulating a number of intracellular messengers. Some actions of GABA are associated with an increase in membrane conductance to Cl- ions and are antagonized by the GABA antagonists bicuculline and Picrotoxin. Receptors mediating these effects are referred to as GABAA receptors and have been investigated intensively, especially because of their close association to the benzodiazepine and barbiturate binding sites. More recently, presynaptic bicuculline-insensitive actions of GABA have been discovered by Bowery and his colleagues, who opened up a new field of investigation (see Bowery, 1982). These actions are mediated by GABAB receptors, which are specifically activated by the GABAB agonists baclofen and 3-aminopropylphosphonic acid. We describe in this chapter recent data concerning the presynaptic actions mediated by GABAB receptors in the hippocampus. We first briefly summarize the better known postsynaptic effects of GABAB receptor activation.
KeywordsDepression Adenosine Guanine Monophosphate Pertussis
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- Bowery NG (1982): Baclofen: 10 years on. TiPS 3:400–403Google Scholar
- Cruelli V, Haby M, Jassik-Gerschenfeld D, Leresche N, Pirchio M (1988): Cl- and K+-dependent inhibitory postsynaptic potentials evoked by interneurons of the rat lateral geniculate nucleus. J Physiol 399:153–176Google Scholar
- Dutar P, Rascol O, Lamour Y (1989): ω-conotoxin GVIA blocks synaptic transmission in the CA1 field of the hippocampus. Eur J Pharmacol 174:261–266Google Scholar
- Karbon EW, Enna SJ (1989): GABAB receptors and the augmentation of neurotransmitter-stimulated cyclic AMP production. In: GABA: Basic Research and Clinical Applications, Bowery NG, Nistico G, eds. Pythagora Press Rome, MilanGoogle Scholar
- Nicoli RA, Malenka RC, Kauer JA (1990): Functional comparison of neurotransmitter receptor subtypes in mammalian central nervous system. Physiol Rev 70:513–565Google Scholar
- Nicoli RA, Dutar P (1989): Physiological roles of GABAA and GABAB receptors in synaptic transmission in the hippocampus. In: Allosteric Modulation of Amino Acid Receptors: Therapeutic Implications, Barnard EA, Costa E, eds. New York: Raven PressGoogle Scholar
- Raiteri M, Bonanno G, Fedele E (1989a): Release of γ-[3H]aminobutyric acid (GABA) from electrically stimulated rat cortical slices and its modulation by GABAB autore-ceptors. J Pharm Exp Ther 250:648Google Scholar
- Solis JM, Nicoli RA (1992): Pharmacological characterization of GABAB mediated responses in the CA1 region of the rat hippocampal slice. J Neuro sci 12:3466–3472Google Scholar
- Waldmeier PC, Wicki P, Feldtrauer JJ, Baumann PA (1988): Potential involvement of a (—)-baclofen-sensitive autoreceptor in the modulation of the release of endogenous GAB A from rat brain slices in vitro. Naunyn-Schmiedebergs Arch Pharmacol 377:289–295Google Scholar
- Wojcik WJ, Paez X, Ulivi M (1989): A transduction mechanism for GABAB receptors. In: Allosteric Modulation of Amino Acid Receptors: Therapeutic Implications, Barnard EA, Costa E, eds. New York: Raven PressGoogle Scholar