Information processing in mammalian gustatory systems.

The taste system has multiple functions that are carried by three cranial nerves. It is now apparent that these functions cannot be accommodated by a single coding mechanism for taste quality. A current view emphasizes the likely existence of coding channels activated by specific sets of receptors.     

Metabolic feedback in mammalian endocrine systems.

Information processing through feedback loops is an integral part of most endocrine systems, and ranges from simple negative loops to complex combinations of negative and positive loops. Moreover, feedback may occur at local (paracrine) or long-distance sites, and with multiple time-domains. Traditionally, feedback is visualized as one hormone stimulating release of a second hormone, which then circulates in the blood to carry out various biological activities, one of which is to inhibit further secretion of the first hormone. This represents a fail-safe mechanism to protect the organism against the potentially damaging effects of uncontrolled secretion of many of the common hormones, some of which are highly catabolic or anabolic. However, it is becoming increasingly apparent that the products of catabolism and anabolism may themselves participate in the feedback process in either a feed-forward or feedback manner. For example, free fatty acids are liberated by the action of growth hormone, and in turn are potent inhibitors of growth hormone secretion (feedback). On the other hand, stress activates adrenal cortical and medullary secretion, which also promotes lipolysis, but in this case the liberated free fatty acids may actually stimulate the system further (feed-forward). Similarly, glucose has been shown to directly inhibit the activity of several different endocrine pathways, and must now be considered an integral part of the overall regulatory mechanism involved in fine-tuning secretion and possibly production of hormones. By constructing models of feedback of increasing complexity, it is possible to make predictions about previously unrecognized relationships between hormones and products of metabolism.     

Inhibitory Effects of 2-Deoxy-D-glucose on Methanol Metabolism in Torulopsis sp.

Inhibitory effects of 2-deoxy-D-glucose (2dG) on methanol metabolism in Torulopsis A–12 were investigated. The remarkable inhibition was observed on growth in the presence of 50 μg/ml of 2dG when methanol was used as a carbon source. At the earlier time of incubation with 2dG, the incorporation of ¹⁴C-methanol into hexose-phosphate by intact cells was inhibited by 2dG, and this led to the reduction of the intracellular concentration of hexose-phosphates. In the later period of incubation the specific activity of alcohol oxidase reduced, and formate accumulated extracellularly.     

Inhibitory action of melatonin on a pineal antigonadotropin.

An acidic extract of bovine pineal glands, partially purified by gel chromatography, yielded two distinct fractions which inhibited compensatory ovarian hypertrophy in mice. When the fractions were tested for antigonadotropic properties in the presence of melatonin only one fraction was found to be effective. Melatonin by itself and no stimulatory effect on COH, suggesting that melatonin blocked the antigonadotropic activity of the one fraction.     

The function of Ca+ in the action of mammalian collagenases.

The removal of extrinsic Ca²⁺ from human skin, rat skin, and postpartum rat uterus collagenases results in a reversible loss of enzymatic activity, which becomes irreversible with increasing length of Ca²⁺-free incubation at physiological temperature and pH. Ca²⁺ is necessary for thermostabilization both in the presence and absence of the collagen substrate. Enzymes from all three sources display linear rates of reaction at Ca²⁺ concentrations from 0.5 to 20 mm and are half-maximally activated at 0.5 mm Ca²⁺. The increase in collagenase activity with increasing Ca²⁺ concentration is associated with an increase in thermostabilization. Ba²⁺ and Sr²⁺ are effective substitutes for Ca²⁺ in human skin collagenase but not in the collagenases from rat tissues. These studies also indicate that Ca²⁺ plays no role in the binding of collagenases to their substrate.     

Inhibitory action of marine algae extracts on the Trypanosoma cruzi dihydroorotate dehydrogenase activity and on the protozoan growth in mammalian cells

Trypanosoma cruzi, the causative agent of Chagas' disease, replicates in mammalian cells and relies on the de novo pyrimidine biosynthetic pathway that supplies essential precursors for nucleic acid synthesis. The protozoan dihydroorotate dehydrogenase (DHOD), the fourth enzyme of the pathway catalyzing production of orotate from dihydroorotate, markedly differs from the human enzyme. This study was thus aimed to search for potent inhibitors against T. cruzi DHOD activity, and a number of methanol extracts prepared from green, brown, and red algae were assayed. The extracts from two brown algae, Fucus evanescens and Pelvetia babingtonii, yielded 59 and 58% decrease in the recombinant DHOD activity, respectively, at the concentration of 50 microg/ml. Inhibition by these extracts was noncompetitive with respect to dihydroorotate, with apparent Ki values of 35.3+/-5.9 and 10.3+/-4.4 microg/ml, respectively. Further, in an in vitro T. cruzi-HeLa cell infection system, ethanol-reconstituted F. evanescens and P. babingtonii extracts at the concentration of 1 microg/ml, respectively, decreased significantly the infection rate of host cells and the average parasite number per infected cell. These results imply that F. evanescens and P. babingtonii contain inhibitor(s) against the T. cruzi DHOD activity and against the protozoan infection and proliferation in mammalian cells. Identification of inhibitor(s) in these two brown algae and further screening of other marine algae may facilitate the discovery of new, anti-trypanosomal lead compounds.     

Inhibitory action of virginiamycin components on cell-free systems for polypeptide formation from Bacillus subtilis

Although virginiamycin components VM and VS are known to exert in vivo a synergistic inhibition of bacterial growth and viability, in cell-free systems only VM has proven active. In the present work, the in vivo and in vitro activities of VM and VS on Bacillus subtilis have been compared.Peptide formation in homogenates of bacteria previously incubated with either VM or VS was found strongly repressed; the 2 components acted synergistically. Ribosomes were fully responsible for this effect, as shown by mixed reconstitution experiments. On the other hand, cytoplasm from control bacteria disrupted in 10 mM Mg²⁺ buffer was refractory to in vitro inhibition by virginiamycin, whereas ribosomes prepared in 1 mM Mg²⁺ were sensitive to VM. VS was inactive on poly(U)-directed poly(phenylalanine) formation, and displayed some activity on the poly(A)-poly(lysine) system. In a cell-free system from Bacillus subtilis infected with phage 2C, both VM and VS were active and blocked synergistically protein synthesis in vitro. When the host cells were incubated with VS and the corresponding homogenate was then treated with VM, a complete inhibition of protein synthesis was observed. The present work, thus, describes the techniques for investigating the in vivo and in vitro action of synergimycins on the same organism, and for reproducing in vitro the synergistic interaction of type A and B components previously observed only in vivo.Abbreviations poly(U) poly(uridylic acid) - poly(A) poly(adenylic acid) - VM and VS the M and S components of virginiamycin - pfu plaque forming units     

Inhibitory mechanisms of Maillard reaction products

In order to determine the inhibitory mechanism of antibacterial Maillard reaction products (MRP), heated mixtures containing arginine and xylose (AX) or histidine and glucose (HG) were studied for their mutagenic effect, using the Salmonella mutagenic test system ('Ames test'), with regard to their effect on the uptake of serine, glucose and oxygen and for their effect on iron solubility. It was found that the MRPs tested had little or no mutagenic effect, while an inhibitory effect on the uptake of serine, glucose and oxygen was observed. The MRPs also had an effect on the solubility of iron in nutrient broth and in phosphate buffer. While the AX mixture reduced the solubility of iron it was increased by the HG mixture. The reduction of iron solubility in the presence of the AX mixture was much greater at pH 8 than at pH 5. The present data suggest that the antibacterial effect of the MRPs tested is primarily due to the interaction between MRPs and iron, resulting in reduced oxygen uptake.