Nitric oxide controls oscillatory activity in thalamocortical neurons.

Nitric oxide (NO) is considered a diffusible messenger involved in neuronal communication, although the post-synaptic target cells of NO action and the associated biological function in the CNS are still a matter of controversy. Within the discrete pattern of NO-synthesizing neurons in the brain, NO synthase is specifically colocalized with the cholinergic brain stem-thalamic system, which is thought to regulate the state-dependent activity of the thalamocortical circuit. Here we report evidence indicating that the release of NO onto thalamocortical neurons results in an alteration in voltage dependence of the hyperpolarization-activated cation conductance, probably mediated via the cGMP system. NO selectively dampens oscillatory neuronal activity, indicating a rapidly diffusing signaling mechanism that controls the functional state of the thalamocortical network.     

Inhibition of chymase activity by phosphoglycerides

The activity of chymase was markedly inhibited by phosphoglycerides such as phosphatidic acid, phosphatidylserine, and phosphatidylinositol, but was not affected by acylglycerides, phosphoglyceroserine, serine, inositol, or glycerol. These results suggest that both the nonpolar hydrophobic hydrocarbon tails and the polar hydrophilic head are essential for the inhibitory effects of phosphoglycerides. Binding of a primary amine to an anionic polar head of phosphatidic acid, such as in phosphatidylserine and phosphatidylethanolamine, slightly decreased the inhibitory effect of phosphatidic acid and, conversely, binding of a strong cation to the head, such as in phosphatidylcholine, resulted in its activation of chymase. Phosphatidic acid containing an unsaturated fatty acid, such as dioleoyl phosphatidic acid, caused the same extent of inhibition as natural phosphatidic acid from bovine brain, but was 20 times more inhibitory than phosphatidic acid containing a saturated fatty acid, such as distearoyl phosphatidic acid. The inhibition by phosphatidylserine was noncompetitive and pseudoirreversible, and the K_i value was 0.54 μm. The inhibition of chymase by phosphatidylserine was pH dependent, being strong at pH 8.5 to 9.5 but weak below pH 7.5. Phosphatidylserine specifically inhibited chymase and elastase; it did not inhibit the other chymotrypsin-type serine endopeptidases tested, trypsin, papain, collagenase, carboxypeptidase A, or cathepsin D.     

Functional convergence of response properties in the auditory thalamocortical system

One of the brain's fundamental tasks is to construct and transform representations of an animal's environment, yet few studies describe how individual neurons accomplish this. Our results from correlated pairs in the auditory thalamocortical system show that cortical excitatory receptive field regions can be directly inherited from thalamus, constructed from smaller inputs, and assembled by the cooperative activity of neuronal ensembles. The prevalence of functional thalamocortical connectivity is strictly governed by tonotopy, but connection strength is not. Finally, spectral and temporal modulation preferences in cortex may differ dramatically from the thalamic input. Our observations reveal a radical reconstruction of response properties from auditory thalamus to cortex, and illustrate how some properties are propagated with great fidelity while others are significantly transformed or generated intracortically.     

Electrical activity of thalamocortical association systems in postnatal ontogeny of the cat

Electrical responses to somatic, photic, and acoustic stimulation in the sensomotor, parietal, temporal, and occipital regions of the cortex were studied in the nucleus lateralis posterior and nucleus ventralis lateralis of the thalamus by recording averaged evoked potentials in kittens (aged 3 to 41 days) anesthetized with pentobarbital. A definite order of maturation of afferent inputs into cortical association areas was demonstrated. The parietal cortex was shown to become polysensory before the sensorimotor cortex. It is suggested that the nucleus lateralis posterior is the main thalamic nucleus responsible for conduction of visual information to the cortex in kittens during the first month of life. Incorporation of this nucleus into the system conducting somatic impulsation to the sensorimotor cortex takes place by the age of 3 weeks.A. A. Zhdanov Leningrad State University. Translated from Neirofiziologiya, Vol. 14, No. 5, pp. 476–482, September–October, 1982.     

Inhibition of macrophage tumoricidal activity by glucocorticoids

In this study, the effect of corticosteroids on the activation of macrophages to a fully tumoricidal state was examined. Thioglycolate-elicited peritoneal exudate macrophages from C3H/HeJ mice were rendered cytolytic for P815 mastocytoma cells in a two-signal tumoricidal assay that used recombinant interferon-gamma (rIFN-gamma; 1 to 10 U/ml) as a "priming" signal and butanol-extracted lipopolysaccharide (But-LPS; 0.1 to 5 micrograms/ml) as a "trigger" signal. Treatment of macrophages with either rIFN-gamma alone or But-LPS alone failed to result in significant cytolytic ability. Tumoricidal activity was markedly inhibited in a dose-dependent fashion when glucocorticoids were added simultaneously to the cultures with rIFN-gamma and But-LPS at concentrations ranging from 1 X 10(-10) to 1 X 10(-5) M. Nonglucocorticoid sex hormones failed to inhibit tumoricidal activity in this system under identical culture conditions. Inhibition was most effective if the glucocorticoids were added simultaneously with the priming and triggering signals (rIFN-gamma and But-LPS); however, if the glucocorticoids were added 24 hr after the signals were provided to the cultures, suboptimal inhibition was observed. Experiments that dissociated the priming phase of activation from the triggering phase showed that glucocorticoids inhibited both the rIFN-gamma-induced priming stage as well as the But-LPS-induced triggering stage of activation. These observations provide evidence that glucocorticoids, but not other steroid hormones, inhibit the activation of macrophages to a fully tumoricidal state by interfering with either the priming or triggering signals in this two-signal model of macrophage activation.     

Inhibition of voluntary activity by growth hormone

During food deprivation and subsequent refeeding there are alterations in growth hormone (GH) secretion and wheel-running activity such that wheel running increases when GH secretion decreases and vice versa. To investigate if there might be a causal relationship between GH secretion and wheel running, the effect of GH administration on wheel running was studied. Female Sprague-Dawley rats were placed singly in activity-wheel cages shortly after weaning. Beginning at 70–75 days of age the rats received 14 daily control injections of saline followed by 14 daily injections of GH and a further 14 days of control injections. Wheel-running activity was inhibited during the period of growth hormone injections. Possible implications of this result are discussed.     

Inhibition of lipase activity by low-molecular-weight chitosan

Inhibition of enzymatic activity of lipase (EC 3.1.1.3) from the fungus Candida rugosa and wheat (Triticum aestivum L.) germ by low-molecular-weight chitosan with an average molecular weight of 5.7 kDa in reactions of p-nitrophenyl palmitate cleavage was studied. Preincubation of lipases with chitosan, prior to addition of the substrate to solution, showed that equilibrium during the lipase-inhibitor complex formation was reached within 30 min. The inhibition constants for C. rugosa lipase and wheat germ lipase were 1.4 and 0.9 mM, respectively. The contribution of electrostatic interactions to the complex formation between chitosan and lipases is insignificant.     

Inhibition of cathelicidin activity by bacterial exopolysaccharides

The interaction of bacterial exopolysaccharides, produced by opportunistic lung pathogens, with antimicrobial peptides of the innate primate immune system was investigated. The exopolysaccharides were produced by Pseudomonas aeruginosa , Inquilinus limosus and clinical isolates of the Burkholderia cepacia complex, bacteria that are all involved in lung infections of cystic fibrosis patients. The effects of the biological activities of three orthologous cathelicidins from Homo sapiens sapiens , Pongo pygmaeus (orangutan) and Presbitys obscurus (dusky leaf monkey) were examined. Inhibition of the antimicrobial activity of peptides was assessed using minimum inhibitory concentration assays on a reference Escherichia coli strain in the presence and absence of exopolysaccharides, whereas complex formation between peptides and exopolysaccharides was investigated by means of circular dichroism, fluorescence spectroscopy and atomic force microscopy. Biological assays revealed that the higher the negative charge of exopolysaccharides the stronger was their inhibiting effect. Spectroscopic studies indicated the formation of molecular complexes of varying stability between peptides and exopolysaccharides, explaining the inhibition. Atomic force microscopy provided a direct visualization of the molecular complexes. A model is proposed where peptides with an α-helical conformation interact with exopolysaccharides through electrostatic and other non-covalent interactions.     

Inhibition of cellulase activity by sun_ower polyphenols

The cellulase-inhibitor binding constant (b) for chlorogenic, ferulic, caffeic and sinapic acids, when these compounds were present in the range of concentrations found during the aqueous extraction of sun_ower oil, was calculated. Chlorogenic acid presented a weak inhibiting power (b = 0.14 L/mmol), whereas sinapic acid conducted as the strongest inhibitor (b = 14.60 L/mmol). The inhibition effects were not additive, since in the presence of mixtures the enzyme retained 75-85% of its activity.     

Inhibition of soil urease activity by aminocresols

Summary The effect on soil urease activity of five aminocresols, at concentrations of 5–100 g/g soil, was examined in the laboratory. Two compounds, 4-amino-o-cresol and 4-amino-m-cresol, significantly inhibited urease activity. The efficacy of 4-amino-o-cresol was compared with that of phenylphosphorodiamidate (PPDA), a known inhibitor, in three U.K. soils. At 50g/g soil 4-amino-o-cresol was as inhibitory as an equivalent concentration of PPDA in a soil with low urease activity, but was less inhibitory in two soils with high urease activity.     

Inhibition of lipase activity by low-molecular-weight chitosan

Inhibition of enzymatic activity of lipase (EC 3.1.1.3) from the fungus Candida rugosa and wheat (Triticum aestivum L.) germ by low-molecular-weight chitosan with an average molecular weight of 5.7 kDa in reactions of p-nitrophenyl palmitate cleavage was studied. Preincubation of lipases with chitosan, prior to addition of the substrate to solution, showed that equilibrium during the lipase-inhibitor complex formation was reached within 30 min. The inhibition constants for C. rugosa lipase and wheat germ lipase were 1.4 and 0.9 mM, respectively. The contribution of electrostatic interactions to the complex formation between chitosan and lipases is insignificant.     

Inhibition of serum oxytocinase activity by prostaglandins

The effect of prostaglandins (PGs) and other compounds on human serum oxytocinase (EC 3.4.11.3) activity in vitro was studied by a sensitive assay using S-berizyl-l-cysteine-p-nitroanilide as substrate. PGE₁, PGE₂ and PGF_2α significantly inhibited serum oxytocinase activity in a dose-related manner and in decreasing order of potency. cGMP, 8-bromo-cGMP, indomethacin, polyphloretin phosphate, hypertonic saline and urea were also active. cAMP, db-cAMP, 8-bromo-cAMP, db-cCMP, 5′-AMP, 5′-ADP, 5′-ATP, 5′-GDP, 5′-GTP, aspirin, sodium salicylate, paracetamol, theophylline and IBMX did not inhibit the enzyme activity. The results suggest that the oxytocic action of prostaglandins may be due, at least in part, to an inhibition of oxytocinase activity.