Receptors & channels最新文献

Effective screening of large compound libraries in ion channel drug discovery requires the development of new electrophysiological techniques with substantially increased throughputs compared to the conventional patch clamp technique. Sophion Bioscience is aiming to meet this challenge by developing two lines of automated patch clamp products, a traditional pipette-based system called Apatchi-1, and a silicon chip-based system QPatch. The degree of automation spans from semi-automation (Apatchi-1) where a trained technician interacts with the system in a limited way, to a complete automation (QPatch 96) where the system works continuously and unattended until screening of a full compound library is completed. The performance of the systems range from medium to high throughputs.

Levels of 19 proteinous amino acids and of total free amino acids were assayed by gas-liquid chromatography in cytosols of rat atrial and ventricular heart muscle cardiomyocytes. These amino acids were assayed after the rats had been exposed to either exercise (swimming) or hypoxia (hypobaric pressure of 686 hectoPascals). Out of the total free amino acids levels of arginine, glutamine and cysteine in atrial and ventricular cardiac muscle cytosols of control rats were the highest of all amino acids assayed. The control levels of all other amino acids assayed in atrial or ventricular cardiac muscles ranged from 0.1% to 10.6% of the total free amino acids in the control rats. Physical stress (exercise and hypoxia) significantly reduced the total amount of cytosolic free amino acids in both heart muscles. While hypoxia decreased the levels of arginine in both heart muscles, exercise abolished the level of cysteine in the atrial heart muscle. Decrease in arginine levels, and elimination of cysteine from the heart's atrial muscle after physical stress, may be attributed to its utilization of nitric oxide and to its synthesis of atriopeptin and/or endothelin during stress. No change was recorded in either experimental group in the level of glutamine in heart muscle cytosol. Exercise and hypoxia affect, in different modes, the levels of all other amino acids assayed, except for tryptophan, tyrosine, and histidine, which are precursors of endogenous neurotransmitters. The impact of proteinous amino acids on some bodily functions is discussed.

Barbituric acid is the parent compound of a large family of hypnotic barbiturates. A nitrogen mustard (N-mustard) group (-CH2CH2N[CH2CH2Cl]2) was placed onto the two nitrogen atoms at positions 1 and 3 of the pyrimidine ring. This N-mustard agent is a solid at 25 degrees C, stable at -10 degrees C for >10 weeks, and soluble in aqueous solvent at 37 degrees C and 25 degrees C. The partition coefficients miLog P and CLog P were calculated to be -0.93 and -1.441 for barbituric acid. The miLog P and CLog P for the N-mustard agent were 1.82 and 2.707, respectively. The N-mustard substituents significantly increased solubility in lipid by-layers. The N-mustard agent alkylated a nucleophilic primary amine (p-chloroaniline) at physiological conditions of pH 7.4 and 37 degrees C. Aliquots of reaction mixtures were withdrawn at known time periods to react with fluorescamine for determination of unreacted p-chloroaniline and calculation of rate constants. The alkylation of the primary amine was second order with rate = k2[Nu]2, (Nu is nucleophile) and rate constant k2 = 0.01358 L/(mole.min). The molecular dipole of barbituric acid and the N-mustard agent was calculated by SPARTAN software (wavefunction, Irvine, CA) to be 0.681 and 2.153 Debye, respectively. The brain/blood partition coefficient (Log BB) of the N-mustard agent was -0.399. Values of molecular polar surface area (TPSA) for barbituric acid and the N-mustard agent was 75.27 and 64.17, respectively. TPSA values indicate an expected intestinal absorbance to be 79% and 90%, respectively. The N-mustard agent showed zero violations of the Rule of 5, indicating good bioavailability.

Potassium channels govern the permeability of cells to potassium ions, thereby controlling the membrane potential. In metazoa, potassium channels are encoded by a large, diverse gene family. Previous analyses of this gene family have focused on its diversity in mammals. Here we have pursued a more comprehensive study in Caenorhabditis elegans, Drosophila melanogaster, and mammalian genomes. The investigation revealed 164 potassium channel encoding genes in C. elegans, D. melanogaster, and mammals, classified into seven conserved families, which we applied to phylogenetic analysis. The trees are discussed in relation to the assignment of orthologous relationships between genes and vertebrate genome duplication.