The neuroactive compound, gamma-hydroxybutyrate (GHB), has been found to inhibit cAMP formation in homogenates from rat brain. To determine in which cell type this effect occurs we have studied the influence of GHB on cAMP formation in both neurons and astroglial cells in primary culture. In neurons, in the presence of theophylline, GHB inhibits cAMP formation. In astroglial cells GHB also inhibits cAMP formation in the presence of theophylline, whereas, in the absence of theophylline, it stimulates cAMP formation. The effect of GHB on cAMP formation reinforces the similarity between GHB and the opioid peptides. Work on the purification and characterization of the mitochondrial hydroxyacid-oxoacid transhydrogenase has continued. The kinetic properties of the enzyme which catalyzes the initial rate-limiting step of gamma-hydroxybutyrate oxidation in the mitochondrial fraction of the cell are being determined. These studies will include the kinetics of other substrates of this enzyme such as gamma-ketoglutarate and L-beta- hydroxybutyrate. These results will be of interest since this is the first report of a hydroxyacid-oxoacid transhydrogenase in mammalian tissue. It is also the first report of an enzyme which can catalyze the oxidation of L-beta-hydroxybutyrate.
