Electrophysiological properties of pyridine receptors in the crayfish walking leg

Summary Responses of pyridine sensitive units on walking legs of the crayfishOrconectes limosus have been studied using extracellular recording techniques.Post-stimulus-time histograms were established and the mean values of the maximal frequencies were plotted in dose-response curves. The curves can be separated into two groups having a slope of 0.3 and 1 in double logarithmic plots and a sensitivity range of 4 and 2 decades, respectively. This implies two different types of pyridine receptors.Abbreviation vH van Harreveld solution     

Characteristics of single chemoreceptive units sensitive to amino acids and related substances in the crayfish leg

Summary Impulses in single afferent fibres from amino acid receptors were recorded extracellularly. Doseresponse relations were determined for different superfused amino acids; the relations all had a slope of 1, a common saturation level, and the action of different amino acids was characterized by a specific half saturation concentration,K _M. The most effective amino acids were always L-serine, L-alanine and L-histidine, having aK _M of 10^–5, 2·10^–5 and 1.5·10^–4 mol/l, respectively. The sequence of effective amino acids was the same for all units tested. Structural requirements for optimal stimulatory action of the amino acid molecules were concluded.Abbreviation vH van Harreveld solution This work was supported by the Deutsche ForschungsgemeinschaftWe gratefully acknowledge assistance in electronics from Mr. W. Zeitz, and in mechanics from Mr. D. Beyer and Mr. L. Müller. Technical help was provided by Mrs. E. Köster, secretarial help by Mrs. L. Bauer.     

Electrophysiological studies of pyridine-sensitive units on the crayfish walking leg

Summary Pyridine-sensitive units located on the walking legs of the crayfishAustropotamobius torrentium were studied by extracellular recording of the action potentials of single afferent fibers. To characterize the sensitivity and specificity of the pyridine receptor, 79 pyridine analogs and other related substances were tested on 70 neurons. The maximum impulse frequency of the response was used to construct dose-response curves. The effectiveness of stimulatory substances was characterized at the half-maximal-response frequency, K_M. The effectiveness rank order of the substances was found to be the same for all units tested. The most effective substances were: pyrazinecarboxamide > 3-acetylpyridine > nicotinamide > pyridine-3-aldoxime, with K_M values of 1.5×10^–6, 4× 10^–6, 10^–5 and 4 x 10^–5 mol/1, respectively. The inferred structural requirements for an optimal stimulatory molecule are that it have a N-containing aromatic ring system with a specific substituent in them position.     

Rat plasma levels of amino acids and related compounds during stress

Forty-one amino acids and related compounds were measured (using an HPLC physiological amino acid analysis procedure fully validated for plasma studies) in rat plasma obtained through an indwelling jugular catheter before, during and following a 30 min period of immobilization. Taurine, phosphoethanolamine, aspartic acid, glutamic acid, alanine, cystine, tyrosine, beta-alanine and ethanolamine were increased during the period of stress; whereas, valine, tryptophan and arginine were decreased. Most of these alterations were restored toward normal during the 30 min of rest following the stress period. However, cystine, ethanolamine and beta-alanine remained significantly elevated, and valine, tryptophan and arginine remained significantly reduced. Serine, isoleucine, leucine and glutamine were not significantly altered during the stress period, but became significantly reduced during the 30 min following the stress period. While the patterns of amino acid alterations were generally consistent from animal to animal, the magnitude of the responses were variable with some rats demonstrating much larger responses than others. These results may implicate amino acids as important markers for stress related pathologies. The individual differences noticed may explain why some individuals show more stress effects than others.     

Hibernation hypothermia and metabolism in hedgehogs--changes in free amino acids and related compounds

1. Hypothermia in midwinter revealed a marked increase in GABA and glutamine due to active decarboxylation and amidation of glutamic acid. This influenced the glutamate-aspartate pathway and resulted in a significant drop in levels of both acids. 2. Elevated levels of GABA and taurine during hibernation pointed to their role as inhibitory neurotransmitters. 3. Amidation of glutamate induced a noticeable drop in ammonia concurring with increased urea and low uric acid levels. 4. Hypothermia in summer revealed a significant role of temperature as a determining factor in the hibernation cycle. Arousal was a repeated, though reversed, phenomenon in this cycle.     

Temperature dependence of the response of the pyridine-sensitive units in the crayfish walking leg

Summary The responses of single pyridine-sensitive neurons ofAustropotamobius torrentium (formerlyOrconectes limosus) to pyridine were recorded extracellularly at different temperatures of the bath solution (between 6–30 °C). There was marked temperature dependence of the receptor response with a Q₁₀ of about 4, which was independent of the stimulus concentrations. With prolonged exposure to temperatures >22 °C the initially uniform discharge gives way to rhythmical bursts of action potentials. A characteristic hysteresis loop was obtained with an up-and-down temperature step program. In conformity with previous studies, an effect of ambient temperature on the time course and amplitude of action potentials was found. The results show that the spontaneous activity of the pyridine-sensitive neurons was not influenced by temperature changes. Evidently the temperature dependence of the response of pyridine receptors is based on a mechanism quite different from that underlying the properties of thermoreceptors of other arthropods.Abbreviations H van Harreveld solution - 4-AP 4-aminopyridine - TTX tetrodotoxin - TEA tetraetylammonium     

Antileishmanial activities of dihydrochalcones from piper elongatum and synthetic related compounds. Structural requirements for activity

Two dihydrochalcones (1 and 2) were isolated from Piper elongatum Vahl by activity-guided fractionation against extracellular promastigotes of Leishmania braziliensis in vitro. Their structures were elucidated by spectral analysis, including homonuclear and heteronuclear correlation NMR experiments. Derivatives 3-7 and 20 synthetic related compounds (8-27) were also assayed to establish the structural requirements for antileishmanial activity. Compounds 1-11 that proved to be more active that ketoconazol, used as positive control, were further assayed against promastigotes of Leishmania tropica and Leishmania infantum. Compounds 7 and 11, with a C(6)-C(3)-C(6) system, proved to be the most promising compounds, with IC(50) values of 2.98 and 3.65 microg/mL, respectively, and exhibited no toxic effect on macrophages (around 90% viability). Correlation between the molecular structures and antileishmanial activity is discussed in detail.