Interaction of α-conotoxin ImII and its analogs with nicotinic receptors and acetylcholine-binding proteins: additional binding sites on Torpedo receptor

α-Conotoxins interact with nicotinic acetylcholine receptors (nAChRs) and acetylcholine-binding proteins (AChBPs) at the sites for agonists/competitive antagonists. α-Conotoxins blocking muscle-type or α7 nAChRs compete with α-bungarotoxin. However, α-conotoxin ImII, a close homolog of the α7 nAChR-targeting α-conotoxin ImI, blocked α7 and muscle nAChRs without displacing α-bungarotoxin ( Ellison et al. 2003, 2004 ), suggesting binding at a different site. We synthesized α-conotoxin ImII, its ribbon isomer (ImII iso ), 'mutant' ImII(W10Y) and found similar potencies in blocking human α7 and muscle nAChRs in Xenopus oocytes. Both isomers displaced [¹²⁵I]-α-bungarotoxin from human α7 nAChRs in the cell line GH₄C₁ (IC₅₀ 17 and 23 μM, respectively) and from Lymnaea stagnalis and Aplysia californica AChBPs (IC₅₀ 2.0–9.0 μM). According to SPR measurements, both isomers bound to immobilized AChBPs and competed with AChBP for immobilized α-bungarotoxin ( K _d and IC₅₀ 2.5–8.2 μM). On Torpedo nAChR, α-conotoxin [¹²⁵I]-ImII(W10Y) revealed specific binding ( K _d 1.5–6.1 μM) and could be displaced by α-conotoxin ImII, ImII iso and ImII(W10Y) with IC₅₀ 2.7, 2.2 and 3.1 μM, respectively. As α-cobratoxin and α-conotoxin ImI displaced [¹²⁵I]-ImII(W10Y) only at higher concentrations (IC₅₀≥ 90 μM), our results indicate that α-conotoxin ImII and its congeners have an additional binding site on Torpedo nAChR distinct from the site for agonists/competitive antagonists.     

香港鹅耳枥(桦木科)的群落特征

为保护香港特有植物香港鹅耳枥,基于典型样地调查,对香港鹅耳枥所在群落进行了研究。结果表明,在225 m2的样地内,有维管植物37科66属68种。建群种为香港鹅耳枥,个体高度最高3 m,所在群落植株平均高度0.92 m,分层不明显。位于中国香港岛的香港鹅耳枥处于衰退状态,小个体极少。因此,建议采取就地保护和迁地保护措施,以重建种群。     

Modulation of neuronal evoked responses to the medial septal area of hibernating ground squirrels by some neuropeptides after chronic disconnection between septum and preoptico-hypothalamic structures

Effects of some neuropeptides identified in the brain of hibernators (TSKYR, TSKY, DY) and of monoaminergic neurotransmitters (noradrenaline and serotonin) on responses of the medial septal neurons evoked by intraseptal electrical stimulation were analyzed in slices taken from the ground squirrels with chronic basal undercutting of the septum. Despite the elimination of direct contacts with the preoptic area and afferents ascending in the medial forebrain bundle, the neurons retained almost normal level of reactivity and distribution of the reaction types. The neuropeptides effectively modulated neuronal responses of various types, including oligosynaptic short-latency single-spike responses. The latter were strongly facilitated by the neuropeptides. As a rule, changes in the responses to electrical stimulation were independent of the spontaneous activity shifts (in 78% of the tests). It was suggested that the neuropeptides exert a double influence on the septal neurons: direct nonsynaptic effects on the pacemaker potential responsible for the background activity and modulation of synaptic processes. Our experiments showed that descending influences of the septo-hippocampal system are not crucial for the entrance into the hibernation state and its tonic maintenance. The influences of the thermoregulatory--circadian structures of the preoptico-hypothalamic area determine the paradoxically increased latent excitability of septal neurons that allows the septo-hippocampal system to gate external stimuli and organize arousal of the forebrain during hibernation in case of emergency.     

Supramolecular interactions of solid human serum albumin with binary mixtures of solvent vapors.

Sorption isotherms of organic compounds on solid human serum albumin (HSA) from binary vapor mixtures were determined by gas chromatographic headspace analysis. The shape of sorption isotherms depends on molecular structure of studied sorbates. The 'active' compounds capable to sorb effectively on dry HSA increase the sorption of 'passive' compounds unable to be sorbed by dry HSA in absence of the third component. The critical hydration of HSA is required for sorption activation of 'passive' sorbates if water is taken as 'active' component. Ethanol and acetonitrile exhibit such activation effect without threshold. 'Passive' sorbates are able to produce cooperative activation effect on the sorption of 'active' component. Hydration history effect is observed for sorption on prehydrated HSA and HSA hydrated in situ. Obtained results were interpreted in terms of clathrate formation by 'passive' sorbate (substrate) and 'active' component inside the HSA (receptor) binding centers.     

The cardiotropic, hypometabolic and hypothermic activity of peptide fractions from the tissues of hibernating cold-adapted animals

From tissues of hibernating and active long-tailed ground squirrels and from the brain of cold-adapted Yakut horses, low molecular peptide fractions were obtained which, after injection to albino mice, decreased oxygen consumption and rectal temperature in them. The same fractions exhibited negative chrono- and inotropic effects on isolated hearts of ectothermic and endothermic animals. Fractions from the brain of ground squirrels and the brain of horse exhibited similar pattern of the activity. The activity of fractions was subjected to seasonal changes and depended on the degree of their purification. Provisional intracellular microelectrophysiological analysis of the effect of these fractions on the frequency and strength of contractions in isolated heart was made.