Bicuculline and picrotoxin block γ-aminobutryic acid-gated Cl− conductance by different mechanisms

Summary Using isolated, internally perfused bullfrog dorsal root ganglion cells we have studied the dose-response curves for -aminobutyric acid (GABA) in the presence of internally or externally applied GABA antagonists. With external application of antagonists the inhibition of the GABA current by bicuculline was competitive and that by picrotoxin was noncompetitive. Picrotoxin but not bicuculline blocked when internally perfused.To whom reprint requests should be addressed.Acknowledgments. We thank Drs S. Minakami and S. Yasui for helpful discussions and comments.     

A new semisynthetic ergot peptide alkaloid: DCN 203-922

Summary We report the synthesis, stereochemistry and preliminary pharmacological evaluation of DCN 203-922, a novel ergot alkaloid of the cyclol type, which contains in its peptide moiety the uncommon amino acid L-allo-isoleucine.Part of this paper was reported by this author at the Herbstversammlung der Schweizerischen Chemischen Gesellschaft, Bern, in October 1986.     

Occurrence of thiaminase II inSaccharomyces cerevisiae

Summary It was found that cell-free extracts ofSaccharomyces cerevisiae contain thiaminase II which hydrolyzes thiamine and thiamine analogs. The possible involvement of this enzyme and thiamine-synthesizing enzymes in thiamine production from thiamine antagonists is discussed.30 September 1986Acknowledgments. We thank the late Dr S. Yurugi, Takeda Pharmaceutical Industries, Osaka, for his generous gifts of dimethialium, 2-northiamine, -hydroxyethylthiamine, hydroxymethylpyrimidine, 2-norhydroxymethylpyrimidine and hydroxyethylthiazole. We also thank Prof. H. Nakayama, Yamaguchi Women's College, for his kind supply ofEscherichia coli 70–17 and 26–43.     

Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid

Cellulose is the most abundant renewable carbon resource on earth and is an indispensable raw material for the wood, paper, and textile industries. A model system to study the mechanism of cellulose biogenesis is the bacterium Acetobacter xylinum which produces pure cellulose as an extracellular product. It was from this organism that in vitro preparations which possessed high levels of cellulose synthase activity were first obtained in both membranous and soluble forms. We recently demonstrated that this activity is subject to a complex multi-component regulatory system, in which the synthase is directly affected by an unusual cyclic nucleotide activator enzymatically formed from GTP, and indirectly by a Ca (2+) -sensitive phosphodiesterase which degrades the activator. The cellulose synthase activator (CSA) has now been identified as bis-(3' 5')-cyclic diguanylic acid (5'G3'p5'G3'p) on the basis of mass spectroscopic data, nuclear magnetic resonance analysis and comparison with chemically synthesized material. We also report here on intermediary steps in the synthesis and degradation of this novel circular dinucleotide, which have been integrated into a model for the regulation of cellulose synthesis.