There have been a growing number of observations of oscillating protein levels (p53 and NFkB) in eukaryotic signalling pathways. This has resulted in a renewed interest in the mechanism by which such oscillations might occur. Recent computational work has shown that a multisite phosphorylation mechanism such as that found in the MAPK cascade can theoretically exhibit bistability. The bistable b...

In Parkinson's disease the dopaminergic inhibition--mediated by DA2 receptors in the striatum--is reduced. Therefore glutamatergic excitation predominates in the antero-dorsal striatum. In turn the glutamatergic neurons of the subthalamic nucleus become disinhibited. Antagonists of the NMDA-subtype of glutamate receptors injected locally into the glutamatergically innervated nuclei or competiti...

p-Aminobenzoic and pteroic acids antagonize the inhibition of the growth of psittacosis virus (strain 6BC) by sulfadiazine in a competitive manner. Pteroylglutamic acid exerts a non-competitive type sulfonamide antagonism. The effects of certain analogues of pteroylglutamic acid and of pteroic acid on the growth of psittacosis virus and its inhibition by sulfadiazine are reported. The implicati...

1. The kinetics of the inhibitory action of four different angiotensin-converting enzyme inhibitors was evaluated in vitro with rat lung enzyme and the substrate hippuryl-histidyl-leucine. 2. Enzyme velocity against substrate concentration curves were fitted squares to hyperbolae by a weighted least squares iterative method to obtain apparent values of Km, Vmax. and K/V at each concentration of...

Attachment of radiolabeled M. pneumoniae to human WiDr cell culture monolayers was dependent on the WiDr cell density and the concentration of M. pneumoniae. Saturation of confluent monolayers grown on 5 mm coverslips was attained with only 40 micrograms of M. pneumoniae protein. Preincubating the WiDr monolayers with unlabeled M. pneumoniae or with a protein-rich extract prepared from M. pneum...

It has long been postulated that the dibasic amino acids, lysine, arginine, ornithine, and cystine, share a common renal tubular transport mechanism. This hypothesis has developed from two separate but related lines of evidence. The canine and human renal clearance studies of Pitts, Webber, and Brown (1, 2), Wright et al. (3), Beyer et al. (4), Kamin and Handler (5), and Robson and Rose (6) all...

is strictly non-competitive with 3-phospho-~-glycerate at the catalytic centre and strictly competitive with the corresponding MgATP2-. Analogous product-inhibition patterns were previously obtained with ADP, being non-competitive with MgATPZand competitive with 3-phospho-~-glycerate (Larsson-Rainikiewicz & Arvidsson, 1971). ADP and 1,3-diphospho-~-glycerate appear preferentially to bind to sit...

The ATP-dependent uptake of L-glutamate into synaptic vesicles has been well characterized, implicating a key role for synaptic vesicles in glutamatergic neurotransmission. In the present study, we provide evidence that vesicular glutamate uptake is selectively inhibited by the peptide-containing halogenated ergot bromocriptine. It is the most potent inhibitor of the agents tested: the IC50 was...

Fractions of porcine cerebral cortex extract separated by molecular weight on a Sephadex G-75 column were tested for their activities and potencies to inhibit [3H]benzodiazepine binding to rat brain homogenates. The fractions spanned molecular weights from 500 to 100,000. A potent inhibitor (benzodiazepine-competitive factor I, BCF-I) was discovered in the fraction containing substances with mo...

Calcineurin (protein phosphatase 2B), a calmodulin- and calcium-dependent serine/threonine phosphatase, appears to be regulated by a C-terminal autoinhibitory domain. A 25 amino acid peptide derived from this domain inhibits calcineurin phosphatase activity in vitro. Here we show that a 97 amino acid fragment of the calcineurin A alpha C-terminus is approx. 8-fold more potent than the shorter p...