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  • Gas exchange  (2)
  • Acetylcholine Receptor  (1)
  • Blood brain barrier  (1)
  • 1
    ISSN: 0948-5023
    Keywords: Acetylcholine Receptor ; Acetylcholinesterase ; Modeling ; Receptor ; Homology ; 3-D Structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Acetylcholine is a ligand for both acetylcholinesterases and nicotinic acetylcholine receptors. Hence, at least some local sequence and structural similarities between the acetylcholinesterases and the receptors which recognize acetylcholine (ACh) might be expected. Peterson [2] produced an alignment of the ACh binding region between these two types of ACh–binding molecules, featuring a number of well conserved residues. The extent of this region of sequence similarity suggests the possible existence of a common ancenstral ACh binding module. To attempt to further validate Peterson′s sequence alignment we have built a homology model of the ACh binding domain of the human neuromuscular nicotinic acetylcholine receptor based on the structure of acetylcholinesterase from Torpedo californica. Using this 3–D model we have examined the residues which were previously shown to interact with the endogenous ligand by various methods (mapping, site–directed mutagenesis). The consistency of such data with the model provides further support for a structural similarity and possibly a divergent evolutionary relationship between the ACh–binding domains of these two classes of proteins. Results suggest that this model may be able to contribute to an understanding of the structure and function of the ACh receptor. Using this case as an example, we propose that 3–dimensional computer modeling can be used as a tool to evaluate distant homologies when adequate experimental data (e.g., site–directed mutagenesis) is available.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of comparative physiology 163 (1993), S. 239-246 
    ISSN: 1432-136X
    Keywords: Copper ; Ionoregulation ; Gas exchange ; Cardiovascular function ; Trout, Oncorhynchus mykiss
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Rainbow trout, Oncorhynchus mykiss, acclimated to 33% sea water (12 mg·ml-1 salinity) experienced significant (10 meq·1-1) increases in plasma [Na+] and [Cl-] within 5 h of exposure to 6.3 μmol copper·1-1 indicating severe impairment of branchial ionoregulatory capacity. All plasma ion levels subsequently stabilised once the transbranchial [Na+] gradient was reduced to zero. The similar ionic strength of the external medium and their body fluids appeared to protect trout maintained in 33% sea water from further ionoregulatory stress and any secondary physiological disturbances during exposure to copper. Despite three- and fourfold greater transbranchial [Na+] and [Cl-] gradients, trout acclimated to full-strength sea water (35 mg·ml-1 salinity) suffered no major changes in plasma Na+, Cl-, K+, or Ca2+, blood gases or haematology during 24 h exposure to 6.3 μmol copper·1-1. This reduction in toxicity in full strength sea water cannot be explained by differences in copper speciation. We suggest that during acute exposure to waterborne copper, active NaCl extrusion is unaffected due to the basolateral location of the gill Na+/K+-ATPase, but that ionoregulatory disturbances can occur due to gill permeability changes secondary to the displacement of surface-bound Ca2+. However, in full strength sea water the three-fold higher ambient [Ca2+] and [Mg2+] appear to be sufficient to prevent any detrimental permeability changes in the presence of 6.3 μmol copper·1-1. Plasma [NH + 4 ] and [HCO - 3 ] were both significantly elevated during exposure to copper, indicating that some aspects of gill ion transport (specifically the apical Na+/NH + 4 and Cl-/HCO - 3 exchanges involved in acid/base regulation and nitrogenous waste excretion) are vulnerable to inhibition in the presence of waterborne copper.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of comparative physiology 161 (1991), S. 521-524 
    ISSN: 1432-136X
    Keywords: Transferrin receptors ; Iron transport ; Brain capillaries ; Species specificity ; Blood brain barrier
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The role of specific transferrin (Tf) and Tf receptor interaction on brain capillary endothelial cells in iron transport from the plasma to the brain was investigated by using Tf from several species of animals labeled with 59Fe and 125I, and 15-day and adult rats. The rate of iron transfer was much greater in the 15-day rats. It was greatest with Tf from the mammals, rat, rabbit and human, but much lower with chicken ovotransferrin and quokka (a marsupial), toad, lizard, crocodile, and fish Tf. The uptake of Tf by the brain showed a similar pattern, except for a very high uptake of ovotransferrin (ovo Tf). Iron uptake by the femurs (a source of bone marrow) was also high with Tf from the mammalian species and low with the other types of Tf, but showed little change with aging of the animals. It is concluded that iron transport into the brain is dependent on the function of Tf receptors, probably on capillary endothelial cells, and that these receptors show the same type of species specificity as the receptors on immature erythroid cells. Also, the decrease in iron uptake by the brain as rats age from 15 days to adulthood is specific for the brain and is not a general effect of the aging process.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of comparative physiology 163 (1993), S. 38-47 
    ISSN: 1432-136X
    Keywords: Copper toxicity ; Ionoregulation ; Gas exchange ; Cardiovascular function ; Trout, Oncorhynchus mykiss
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Acutely lethal (24 h) exposure of adult rainbow trout (Oncorhynchus mykiss) to 4.9 μmol copper·l-1 in fresh water (pH 7.9, [Ca2+]≈0.8 mEq·l-1) caused a rapid decline of plasma Na+ and Cl- and arterial O2 tension, and initially a pronounced tachycardia. The internal hypoxia probably resulted from histopathologies observed in the gills of fish exposed to copper, such as cell swelling, thickening and curling of the lamellae, and haematomas. Copper cannot therefore be considered purely as an ionoregulatory toxicant during acutely lethal conditions. Mortality during exposure to copper could not simply be explained by the plasma ionic dilution, nor by the internal hypoxia, since arterial O2 content remained relatively unchanged. Secondary to the ionoregulatory and respiratory disturbances were a number of deleterious physiological responses which included a massive haemoconcentration (haematocrit values as high as 60%) and a doubling of the mean arterial blood pressure. The time-course of these changes suggest that cardiac failure was the final cause of death. In this respect copper exposure resembles low pH exposure in freshwater trout (Milligan and Wood 1982). Copper and H+ appear to be similar in both the primary site of their toxic action (the gills) and the secondary physiological consequences which result from acutely lethal exposures. Furthermore, the acute toxicity syndrome observed may be common to many metals which cause ionoregulatory and/or respiratory problems in freshwater fish.
    Type of Medium: Electronic Resource
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