Selective antagonism by Mg2+ of amino acid-induced depolarization of spinal neurones

Summary In the isolated frog or rat spinal cord, low concentrations of Mg²⁺ (0.5–1.00 mM) markedly depress, in a substantially Ca²⁺-independent manner, ventral root depolarizations produced by dorsal root stimulation and by certain amino acids (e. g. N-methyl-D-aspartate and L-homocysteate) but do not depress depolarizations produced by other excitatory amino acids (e. g. kainate and quisqualate). L-Aspartate-induced depolarizations are more sensitive to Mg²⁺ then are L-glutamate-induced depolarizations.Acknowledgment. We thank D. J. Oakes for skilled technica assistance. This work was supported by the Medical Research Council.     

Characterization of cDNA and genomic clones encoding the precursor to rat hypothalamic growth hormone-releasing factor

Growth hormone-releasing factor (GHRF) is a hypothalamic peptide which positively regulates the synthesis and secretion of growth hormone in the anterior pituitary. The amino-acid sequence of a 43-residue GHRF peptide isolated from rat hypothalamus was recently determined. Immunocytochemical techniques have been used to localize GHRF-containing cell bodies and nerve fibres largely to the medial-basal region of the rat hypothalamus. The rat has also been used extensively as an animal model to study the effects of GHRF on growth hormone synthesis and secretion and on somatic growth. To pursue questions concerning the biosynthesis of GHRF, the expression of the ghrf gene, and its regulation in the hypothalamus by neural and hormonal influences, we have now isolated and characterized both complementary DNA and genomic clones encoding rat hypothalamic GHRF. The rat ghrf gene spans nearly 10 kilobases (kb) of rat genomic DNA, contains 5 exons and encodes a 104-amino-acid precursor to the rat GHRF peptide. Comparison with previously characterized human ghrf cDNA and genomic clones has allowed patterns of conservation of amino-acid and nucleotide sequences between the human and rat GHRFs to be determined.     

Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product

THE superfamily of low molecular mass GTP-binding proteins, for which the ras proteins are prototypes, has been implicated in the regulation of diverse biological activities including protein trafficking, secretion, and cell growth and differentiation. One member of this family, CDC42Hs (originally referred to as Gp or G25K), seems to be the human homologue of the Saccharomyces cerevisiae cell-division-cycle protein, CDC42Sc. A second S. cerevisiae protein, CDC24, which is known from complementation studies to act with CDC42Sc to regulate the development of normal cell shape and the selection of nonrandom budding sites in yeast, contains a region with sequence similarity to the dbl oncogene product. Here we show that dbl specifically catalyses the dissociation of GDP from CDC42Hs and thereby qualifies as a highly selective guanine nucleotide exchange factor for the GTP-binding protein. Although guanine nucleotide exchange activities have been previously described for other members of the Ras-related GTP-binding protein family, this is the first demonstration, to our knowledge, of the involvement of a human oncogenic protein in catalysing exchange activity.     

Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis

Leukotrienes, the biologically active metabolites of arachidonic acid, have been implicated in a variety of inflammatory responses, including asthma, arthritis and psoriasis. Recently a compound, MK-886, has been described that blocks the synthesis of leukotrienes in intact activated leukocytes, but has little or no effect on enzymes involved in leukotriene synthesis, including 5-lipoxygenase, in cell-free systems. A membrane protein with a high affinity for MK-886 and possibly representing the cellular target for MK-886 has been isolated from rat and human leukocytes. Here, we report the isolation of a complementary DNA clone encoding the MK-886-binding protein. We also demonstrate that the expression of both the MK-886-binding protein and 5-lipoxygenase is necessary for leukotriene synthesis in intact cells. Because the MK-886-binding protein seems to play a part in activating this enzyme in cells, it is termed the five-lipoxygenase activating protein (FLAP).     

Diketopiperazines from fermentations: Metabolites,artifacts, or both

Zusammenfassung Es wird gezeigt, dass Diketopiperazine, insbesonderel-Leucyl-l-prolin-anhydrid, eher aus dem Medium stammende Artefakte als echte mikrobielle Stoffwechselprodukte sind.