Co-localization of GABA receptors and benzodiazepine receptors in the brain shown by monoclonal antibodies

The most abundant inhibitory neurotransmitter in the central nervous system, gamma-aminobutyric acid (GABA), exerts its main effects via a GABAA receptor that gates a chloride channel in the subsynaptic membrane. These receptors can contain a modulatory unit, the benzodiazepine receptor, through which ligands of different chemical classes can increase or decrease GABAA receptor function. We have now visualized a GABAA receptor in mammalian brain using monoclonal antibodies. The protein complex recognized by the antibodies contained high- and low-affinity binding sites for GABA as well as binding sites for benzodiazepines, indicative of a GABAA receptor functionally associated with benzodiazepine receptors. As the pattern of brain immunoreactivity corresponds to the autoradiographical distribution of benzodiazepine binding sites, most benzodiazepine receptors seem to be part of GABAA receptors. Two constituent proteins were identified immunologically. Because the monoclonal antibodies cross-react with human brain, they provide a means for elucidating those CNS disorders which may be linked to a dysfunction of a GABAA receptor.     

Structure of mouse kallikrein gene family suggests a role in specific processing of biologically active peptides

The glandular kallikrein gene family comprises 25-30 highly homologous genes that encode specific proteases involved in the processing of biologically active peptides. In the mouse all the members of this family are closely linked on chromosome 7. The 9.5-kilobase nucleotide sequence of a mouse genomic clone contains one complete kallikrein gene (mGK-1), which is expressed in the male mouse submaxillary gland, and the 3' end of another (mGK-2). Differences in the coding potential of these genes and the amino acid sequences of other known kallikreins seem to be functionally related to the substrate specificity of the different enzymes.     

Computed redox potentials and the design of bioreductive agents

Anti-cancer agents that have been made selective for tumour cells by exploiting the known differences in the availability of oxygen between normal and transformed cells are a promising development in cancer chemotherapy. We have recently suggested a new type of bioreductive activity which would depend on a two-electron reduction. For rational design of such compounds, it is essential to be able to predict the redox potentials and the chemical modifications needed to produce the optimum redox value. Calculating redox potentials is a daunting task for the theoretician, however, as the effect of water solvation is clearly of major significance. Recent successful calculations of differences in the free energies of biologically important molecules in aqueous solution using the free-energy perturbation method prompted us to apply the technique to the computation of two-electron redox potentials. The results are accurate to within 20 mV, suggesting that we should be able to manipulate redox potentials by successfully predicting structures with the appropriate value.     

Shape change of blood platelets induced by myelin basic protein

Summary Myelin basic protein (MBP) isolated from bovine spinal cord caused a marked shape change reaction of human blood platelets which was not accompanied by the release reaction and not inhibited by methysergide and spiroperidol. Only those basic proteins, including MBP, which had previously shown to exert neuronal depolarisation also induced the shape change reaction. Therefore, these findings may extend the use of platelets as neuronal models.Acknowledgment. We thank Miss B. Gieux and Miss M. Handschin for skilful technical assistance.