Heteromerization of GABAB Receptors: A New Principle for G Protein-Coupled Receptors. Satellite Symposium to the 28th Annual Meeting of the Society for Neuroscience Los Angeles, CA, November 5–7, 1998

Abstract

The fourth international γ-aminobutyric acid (GABAB) symposium, organized as a satellite meeting to the Annual Society for Neuroscience Meeting in Los Angeles, was the first reunion of the GABAB-receptor community after the long-awaited cloning of a receptor cDNA in early 1997. The organizing committee consisted of N. G. Bowery, J. Gallagher, S. J. Enna, F. Froestl, and H. Bittiger. The symposium included several speakers who joined the GABAB field more recently and many presentations reported studies that made use of the now available genetic tools. In the opening lecture, W. Froestl (Novartis, Basel, Switzerland) outlined the development of radioligands that had been used to clone the first GABAB receptors, GABABR1a and b. Recent data on the structure, function, and distribution of these receptors were summarized by B. Bettler (Novartis, Basel, Switzerland). The two receptors derive from the same gene by alternative N-terminal splicing and share ligand-binding properties and coupling preferences; in addition, their distribution corresponds to the one of native GABAB receptors. In the retina, GABABR1a/b receptors are localized on either side of the synapse, demonstrating that these receptors do not represent exclusive preor postsynaptic subtypes. While the cloned receptors had many of the expected properties, there remained some discrepancies. For example, the coupling of the cloned receptors to presumed effector K and Ca channels in heterologous cells proved surprisingly difficult. Moreover while the antagonist pharmacology of cloned and native GABAB receptors matched neatly, the agonist affinity at the recombinant receptors was drastically reduced. The identification of a second GABAB receptor, GABABR2, now reconciles these puzzling observations. Three representatives of pharmaceutical companies (F. Mar-