Tyrosine residue 271 of the norepinephrine transporter is an important determinant of its pharmacology

The aim was to examine the functional importance in the norepinephrine transporter (NET) of (i) the phenylalanine residue at position 531 in transmembrane domain (TMD) 11 by mutating it to tyrosine in the rat (rF531Y) and human (hF531Y) NETs and (ii) the highly conserved tyrosine residues at positions 249 in TMD 4 of human NET (hNET) (mutated to alanine: hY249A) and 271 in TMD 5, by mutating to alanine (hY271A), phenylalanine (hY271F) and histidine (hY271H). The effects of the mutations on NET function were for uptake of the substrates, examined by expressing the mutant and wildtype NETs in COS-7 cells and measuring the K-m and V-max for uptake of the substrates, [H-3]norepinephrine, [H-3]MPP+ and [H-3]dopamine, the K-D and B-max for [H-3]nisoxetine binding and the K-i of the inhibitors, nisoxetine, desipramine and cocaine, for inhibition of [H-3]norepinephrine uptake. The K-m values of the substrates were lower for the mutants at amino acid 271 than hNET and unaffected for the other mutants, and each mutant had a significantly lower than NET for substrate uptake. The mutations at position 271 caused an increase in the K-i or K-D values of nisoxetine, desipramine and cocaine, but there were no effects for the other mutations. Hence, the 271 tyrosine residue in TMD 5 is an important determinant of NET function, with the mutants showing an increase in the apparent affinities of substrates and a decrease in the apparent affinities of inhibitors, but the 249 tyrosine and 531 phenylalanine residues do not have a major role in determining NET function. (C) 2001 Elsevier Science B.V. All rights reserved.

Effects of Deicing Salt Trace Compounds on Deterioration of Portland Cement Concrete, HR-271, 1987

A study was made of the detrimental effects of trace amounts of calcium sulfate (occurring naturally in halite deposits used for deicing) on portland cement concrete pavements. It was found that sulfate introduced as gypsum with sodium chloride in deicing brines can have detrimental effects on portland cement mortar. Concentrations of sulfate as low as 0.5% of the solute rendered the brine destructive. Conditions of brine application were critical to specimen durability. The mechanisms of deterioration were found to be due to pore filling resulting from compound formation and deposition. A field evaluation of deteriorating joints suggests that the sulfate phenomena demonstrated in the laboratory also operates in the field. A preliminary evaluation was made of remedies: limits on sulfates, fly ash admixtures, treatment of existing pavement, and salt treatments. This report gives details of the research objectives, experimental design, field testing, and possible solutions. Recommendations for further study are presented.

Inconstitucionalidad del artículo 271 de la Ley de Hacienda del Estado de Nuevo León

[Tesis] ( Maestría en Derecho Fiscal ) U.A.N.L.

L'Interdit – no 271, nov./déc. 1979

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