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1.
Kinetic basis for insensitivity to tetrodotoxin and saxitoxin in sodium channels of canine heart and denervated rat skeletal muscle 总被引:10,自引:0,他引:10
The single-channel blocking kinetics of tetrodotoxin (TTX), saxitoxin (STX), and several STX derivatives were measured for various Na-channel subtypes incorporated into planar lipid bilayers in the presence of batrachotoxin. The subtypes studied include Na channels from rat skeletal muscle and rat brain, which have high affinity for TTX/STX, and Na channels from denervated rat skeletal muscle and canine heart, which have about 20-60-fold lower affinity for these toxins at 22 degrees C. The equilibrium dissociation constant of toxin binding is an exponential function of voltage (e-fold per 40 mV) in the range of -60 to +60 mV. This voltage dependence is similar for all channel subtypes and toxins, indicating that this property is a conserved feature of channel function for batrachotoxin-activated channels. The decrease in binding affinity for TTX and STX in low-affinity subtypes is due to a 3-9-fold decrease in the association rate constant and a 4-8-fold increase in the dissociation rate constant. For a series of STX derivatives, the association rate constant for toxin binding is approximately an exponential function of net toxin charge in membranes of neutral lipids, implying that there is a negative surface potential due to fixed negative charges in the vicinity of the toxin receptor. The magnitude of this surface potential (-35 to -43 mV at 0.2 M NaCl) is similar for both high- and low-affinity subtypes, suggesting that the lower association rate of toxin binding to toxin-insensitive subtypes is not due to decreased surface charge but rather to a slower protein conformational step. The increased rates of toxin dissociation from insensitive subtypes can be attributed to the loss of a few specific bonding interactions in the binding site such as loss of a hydrogen bond with the N-1 hydroxyl group of neosaxitoxin, which contributes about 1 kcal/mol of intrinsic binding energy. 相似文献
2.
M Dhananjaya Naidu K Ravindran K S Swami 《Archives internationales de physiologie et de biochimie》1988,96(2):75-79
Male albino rats were treated with insulin for one week (acute) and four weeks (chronic). The lactate dehydrogenase (LDH) activity, lactate and pyruvate levels were estimated in the tissues of experimental and control animals. LDH activity decreased in all the tissues of acute- and chronic treated animals whereas the lactate content is elevated. Pyruvate content also showed increment except in heart and pancreas with reference to acute treatment where it is decreased. The hyperinsulinaemia effect in relation to lacticacidaemia and its influence on energy demand and ammonia secretion is discussed. 相似文献
3.
4.
ISOLATED NERVE ENDINGS (NEUROSECRETOSOMES) FROM THE POSTERIOR PITUITARY : Partial Separation of Vasopressin and Oxytocin and the Isolation of Microvesicles 总被引:5,自引:0,他引:5 下载免费PDF全文
Subcellular fractions of the bovine posterior pituitary, including one composed almost exclusively of pinched-off nerve endings (neurosecretosomes), were characterized electron microscopically, hormonally, and enzymically. 15% of the nerve terminals in the gland were isolated as neurosecretosomes, as estimated from determinations of lactic dehydrogenase, a soluble, cytoplasmic enzyme. Neurosecretosomes were subdivided into three fractions by density-gradient centrifugation. The three subfractions, each shown to be nearly homogeneous populations of neurosecretosomes by means of electron microscopic and enzymic criteria, differed from each other in their vasopressin/oxytocin (VP/OT) ratios. The VP/OT ratio increased from the lightest to the densest fraction, indicating that VP is localized to denser and OT to lighter neurosecretosomes; similar results have been obtained previously for subfractions of neurosecretory granules (NSG). No morphological differences were apparent in neurosecretosomes among the three subfractions. Although complete separation of VP and OT was not achieved, the findings suggest that VP and OT are each stored in a different species of nerve ending and support the hypothesis that a given neurosecretory cell synthesizes, stores, and secretes only one of the peptide hormones. Microvesicles, 40–80 mµ diameter and contained in typical neurosecretory cell terminals, are believed to be degradation products of membrane ghosts of depleted NSG; electron micrographs indicative of this transformation are presented. A fraction rich in microvesicles, but containing some NSG membranes, was prepared by density-gradient centrifugation of an osmolysate of neurosecretosomes. Smaller, apparently nonneurosecretory nerve endings, lacking NSG but filled with small vesicles, are occasionally seen in sections from whole gland. The vesicles in these atypical posterior pituitary nerve endings may be true neurohumor-containing, "synaptic" vesicles. 相似文献
5.
The present study was undertaken to investigate the role of calcium ions (Ca2+) in the induction and secretion of the dengue type 2 virus induced cytotoxic factor and the cytotoxin. This was done by using
calcium channel blocking drugs such as verapamil, nifedipine or diltiazem hydrochloride. The production of cytotoxic factor
was significantly reduced by treatment of dengue type 2 virus infected mice with verapamil. Similarly, a dosedependent inhibition
of the secretion of cytotoxic factor was observed, when spleen cells of the virus-primed mice were treatedin vitro with the 3 calcium channel blockers. The production of cytotoxin by macrophages was abrogated by pretreatment with calcium
channel blockers but had little effect on its secretion as shown by treatment of macrophages with verapamil at 1 h after the
induction to later periods up to 18 h. The findings thus show that in the induction of both the cytokines Ca2+ plays a critical role; on the other hand it is required for the secretion of the cytotoxic factor but not for that of the
cytotoxin. 相似文献
6.
Attenuation of visible light by phytoplankton in a vertically structured ocean: solutions and applications 总被引:1,自引:0,他引:1
Platt Trevor; Sathyendranath Shubha; White George N. III; Ravindran P. 《Journal of plankton research》1994,16(11):1461-1487
To find the solution to problems in applied marine optics, wedo not always need to compute the submarine irradiance at alldepths; in many cases, it is sufficient to know the averageattenuation of light for finite layers of arbitrary thickness.If multiple scattering can be neglected, the average attenuationof light in a finite layer of the water column depends onlyon the vertical distribution of the attenuating substances;in open-ocean waters, the most important of these is phytoplankton.It is shown how the average attenuation of monochromatic lightin an arbitrary layer can be determined when the vertical pigmentprofile takes one of two standardized forms: a shifted Gaussianor a triangle. The choice of efficient algorithms to computethe attenuation in a layer using these models is discussed.The extension to polychromatic light involves the selectionof a function to represent the spectral distribution of thespecific absorption coefficient for phytoplankton, as determinedby observation. Chebyshev polynomial representation is shownto be convenient for applications which require the calculationof a weighted wavelength integral. An efficient procedure forthe evaluation of these integrals, Gauss-Chebyshev quadrature,is presented and evaluated. The extension to the computationof bulk properties for discrete layers is straightforward. 相似文献
7.
Madhu Ramesh Chenikkayala Balachandra Prayasee Baruah Thimmaiah Govindaraju 《Journal of peptide science》2023,29(5):e3465
Liquid–liquid phase separation (LLPS) is a complex physicochemical phenomenon mediated by multivalent transient weak interactions among macromolecules like polymers, proteins, and nucleic acids. It has implications in cellular physiology and disease conditions like cancer and neurodegenerative disorders. Many proteins associated with neurodegenerative disorders like RNA binding protein FUS (FUsed in Sarcoma), alpha-synuclein (α-Syn), TAR DNA binding protein 43 (TDP-43), and tau are shown to undergo LLPS. Recently, the tau protein responsible for Alzheimer's disease (AD) and other tauopathies is shown to phase separate into condensates in vitro and in vivo. The diverse noncovalent interactions among the biomolecules dictate the complex LLPS phenomenon. There are limited chemical tools to modulate protein LLPS which has therapeutic potential for neurodegenerative disorders. We have rationally designed cyclic dipeptide (CDP)-based small-molecule modulators (SMMs) by integrating multiple chemical groups that offer diverse chemical interactions to modulate tau LLPS. Among them, compound 1c effectively inhibits and dissolves Zn-mediated tau LLPS condensates. The SMM also inhibits tau condensate-to-fibril transition (tau aggregation through LLPS). This approach of designing SMMs of LLPS establishes a novel platform that has potential implication for the development of therapeutics for neurodegenerative disorders. 相似文献
8.
Marjon J. H. van Haandel I. M. C. M. Rietjens Ans E. M. F. Soffers Cees Veeger Jacques Vervoort Sandeep Modi Madhu S. Mondal Prasanta K. Patel Digambar V. Behere 《Journal of biological inorganic chemistry》1996,1(5):460-467
The second-order rate constants for the oxidation of a series of phenol derivatives by horseradish peroxidase compound II
were compared to computer-calculated chemical parameters characteristic for this reaction step. The phenol derivatives studied
were phenol, 4-chlorophenol, 3-hydroxyphenol, 3-methylphenol, 4-methylphenol, 4-hydroxybenzoate, 4-methoxyphenol and 4-hydroxybenzaldehyde.
Assuming a reaction of the phenolic substrates in their non-dissociated, uncharged forms, clear correlations (r = 0.977 and r = 0.905) were obtained between the natural logarithm of the second-order rate constants (ln k
app and ln k
2 respectively) for their oxidation by compound II and their calculated ionisation potential, i.e. minus the energy of their
highest occupied molecular orbital [E(HOMO)]. In addition to this first approach in which the quantitative structure-activity
relationship (QSAR) was based on a calculated frontier orbital parameter of the substrate, in a second and third approach
the relative heat of formation (ΔΔHF) calculated for the process of one-electron abstraction and H• abstraction from the phenol derivatives was used as a parameter. Plots of the natural logarithms of the second-order rate
constants (k
app and k
2) for the reaction and the calculated ΔΔHF values for the process of one-electron abstraction also provide clear QSARs with
correlation coefficients of –0.968 and –0.926 respectively. Plots of the natural logarithms of the second-order rate constants
(k
app and k
2) for the reaction and the calculated ΔΔHF values for the process of H• abstraction provide QSARs with correlation coefficients of –0.989 and –0.922 respectively. Since both mechanisms considered,
i.e. initial electron abstraction versus initial H• abstraction, provided clear QSARs, the results could not be used to discriminate between these two possible mechanisms for
phenol oxidation by horseradish peroxidase compound II. The computer calculation-based QSARs thus obtained for the oxidation
of the various phenol derivatives by compound II from horseradish peroxidase indicate the validity of the approaches investigated,
i.e. both the frontier orbital approach and the approach in which the process is described by calculated relative heats of
formation. The results also indicate that outcomes from computer calculations on relatively unrelated phenol derivatives can
be reliably compared to one another. Furthermore, as the actual oxidation of peroxidase substrates by compound II is known
to be the rate-limiting step in the overall catalysis by horseradish peroxidase, the QSARs of the present study may have implications
for the differences in the overall rate of substrate oxidation of the phenol derivatives by horseradish peroxidase.
Received: 29 March 1996 / Accepted: 17 July 1996 相似文献
9.
Abstract: Lateral fluid-percussion brain injury in rats results in cognitive deficits, motor dysfunction, and selective hippocampal cell loss. Neurotrophic factors have been shown to have potential therapeutic applications in neurodegenerative diseases, and nerve growth factor (NGF) has been shown to be neuroprotective in models of excitotoxicity. This study evaluated the neuroprotective efficacy of intracerebral NGF infusion after traumatic brain injury. Male Sprague-Dawley rats received lateral fluid-percussion brain injury of moderate severity (2.1–2.3 atm). A miniosmotic pump was implanted 24 h after injury to infuse NGF (n = 34) or vehicle (n = 16) directly into the region of maximal cortical injury. Infusions of NGF continued until the animal was killed at 72 h, 1 week, or 2 weeks after injury. Animals were evaluated for cognitive dysfunction (Morris Water Maze) and regional neuronal cell loss (Nissl staining) at each of the three time points. Animals surviving for 1 or 2 weeks were also evaluated for neurobehavioral motor function. Although an improvement in memory scores was not observed at 72 h after injury, animals receiving NGF infusions showed significantly improved memory scores when tested at 1 or 2 weeks after injury compared with injured animals receiving vehicle infusions ( p < 0.05). Motor scores and CA3 hippocampal cell loss were not significantly different in any group of NGF-treated animals when compared with controls. These data suggest that NGF administration, in the acute, posttraumatic period following fluid-percussion brain injury, may have potential in improving post-traumatic cognitive deficits. 相似文献
10.
Occurrence of a Lysogenic Streptomyces sp. on the Nodule Surface of Black Gram (Vigna mungo (L.) Hepper) 下载免费PDF全文
A lysogenic Streptomyces sp., strain NS.A4, which was isolated from the nodule surface of black gram (Vigna mungo (L.) Hepper), was found to inhibit rhizobia of fast-and slow-growing strains of cowpeas and soybeans. It exhibited plaques when there was a change in cultural conditions. Repeated culturing of the organism in nutrient agar and broth confirmed the infection of Streptomyces sp. strain NS.A4 by an actinophage. Addition of the culture filtrate of Streptomyces sp. strain NS.A4 to shaken broth cultures of three other Streptomyces spp. resulted in phage infection. 相似文献