ABSTRACT
BACKGROUND & OBJECTIVES: The biochemical mechanisms underlying the development of sensitization-induced airway hyperresponsiveness (AHR) in asthma are poorly defined. Alterations in the regulation of intracellular calcium may play an important role in its pathogenesis. We carried out this study to see the effect of sensitization with ovalbumin on membrane ion fluxes and intracellular calcium in a guinea pig model. METHODS: Airway reactivity to inhaled histamine was measured initially and after sensitization with ovalbumin in 28 guineapigs. Intracellular calcium [Ca(2+)]i was measured in tracheal smooth muscle cells and peripheral leukocytes using fluorescent dye FURA 2AM. Calcium and sodium ion influx across the cell membrane was measured in leukocytes. Ouabain-sensitive Rubidium ((86)Rb) influx was measured in tracheal smooth muscles cells. The activities of Na(+), K(+) ATPase and Ca(2+) ATPase were measured in tracheal smooth muscle cells. Lipid peroxides were measured in plasma. RESULTS: Airway responsiveness was significantly (P<0.001) increased after sensitization along with an increase in [Ca2+]i levels in leukocytes and tracheal smooth muscle cells, higher rates of (45)Ca and (22)Na influx in leukocytes and higher (86)Rb influx rates in tracheal smooth muscle cells, and increased levels of lipid peroxides in plasma. INTERPRETATION & CONCLUSION: In guineapig model of asthma sensitization to allergen increased the membrane permeability to calcium and sodium, and intracellular calcium levels. These alterations may play a role in the pathogenesis of airway hyper-responsiveness following sensitization.
Subject(s)
Animals , Bronchial Hyperreactivity/metabolism , Calcium/chemistry , Cell Membrane/metabolism , Fluorescent Dyes/metabolism , Fura-2/analogs & derivatives , Guinea Pigs , Histamine/metabolism , Ions/metabolism , Leukocytes/cytology , Lipid Peroxidation , Male , Myocytes, Smooth Muscle/cytology , Ovalbumin/metabolism , Rubidium Radioisotopes/metabolism , Sodium Radioisotopes/metabolism , Sodium-Potassium-Exchanging ATPase/metabolism , Trachea/cytologyABSTRACT
Inbred mouse strains vary widely in their susceptibility to the induction of tolerance following oral (intragastric) adminsitation of ovalbumin. Marked differences were found berween strains that form a congenic pair differing at the H-2 complex: C3H/HeJ (H-2K) and C3H.SW(H2b) - which were very susceptible and resitant to tolerance induction, respectively. In comtrast, no significant differences were found betwwwn a/J(H-2a) and A.BY (H-2b) congenics, which were both susceptible, nor among C57BL/10J congenics, which were uniformly resitant to tolerance induction. We conclude that H-2-linked genes determine tolerance susceptibility in conjunction with background genes
Subject(s)
Mice , Rats , Animals , Male , Female , Administration, Oral , /genetics , Intestinal Mucosa/immunology , Ovalbumin/administration & dosage , Mice, Inbred Strains , Drug Tolerance , Enzyme-Linked Immunosorbent Assay , Species Specificity , Intestinal Mucosa/metabolism , Mice, Inbred DBA , Mice, Inbred NZB , Ovalbumin/metabolismABSTRACT
La glucosilación no enzimática de proteínas ha sido implicada en la patogenia de las complicaciones secundarias de la diabetes mellitus. La acetilación reversible de las proteínas por la aspirina podría reducir el avance de la lesión bioquímica. La velocidad de acetilación de la albúmina por la aspirina a 37-C y pH = 7.30 fue determinada y se encontró que ocurría 2 órdenes de magnitud más rápidamente que la glucosilación, proponiendo una base para la posibilidad de tratar con aspirina el avance de las complicaciones secundarias de la diabetes mellitus en pacientes con buen control metabólico
Subject(s)
Humans , Serum Albumin/metabolism , Aspirin/pharmacology , Diabetes Mellitus/complications , Ovalbumin/metabolism , AcetylationABSTRACT
Local anesthetics at a concentration of 10 mM(procaine and lidocaine) were found to inhibit competitively Ca++ binding to lipidextracted RBC membrane, and also to egg albumin film fixed on cover glasses or impregnated into Whatman filter paper (No. 1). A competitive inhibition by local anesthetics was also found in Ca++ binding to Whatman filter paper which had been pretreated with organic solvents to extract possible contaminated lipids. Therefore, it is suggested that the local anesthetics inhibit Ca++ binding not only to phospholipids but to some macromolecules such as membrane proteins, egg albumin film and filter paper.