Relationship between Intracellular Calcium and Airway Reactivity in Guinea Pigs.

Abstract

The regulation of intracellular calcium may play a crucial role in the pathogenesis of asthma because an increase in [Ca 2ϩ ] i is an essential initiating mechanism of cellular activation in inflammatory cells and in airway smooth muscle [1][2][3][4]. Because of the inaccessibility of tracheal tissue in human subjects, animal models have been used to define the biochemical correlates of airway reactivity. Na -ATPase activities in guinea pigs. Because these enzymes serve to lower the intracellular calcium, it was suggested that the higher activities in the more-reactive animals might reflect a compensatory response to higher [Ca 2ϩ ] i level. However, measurements of intracellular calcium were not made. The present study was carried out to examine the relationship between airway reactivity and intracellular calcium. Japanese Journal of Physiology577Japanese Journal of Physiology, 51, 577-583, 2001 Key words: airway hyperreactivity, intracellular calcium, Na-ATPase, lysophosphatidylcholine.Abstract: The present study was carried out to examine the relationship between intracellular free calcium ion concentrations and its regulatory enzymes, sodium potassium adenosine triphosphatase (Na ϩ ,K ϩ -ATPase) and calcium adenosine triphosphatase (Ca 2ϩ -ATPase), with airway reactivity to inhaled histamine in guinea pigs. Forty-nine guinea pigs were included in this study. Of these, 34 animals responded to histamine bronchoprovocation challenge in vivo with a greater than 35% fall in specific airways conductance and were labeled as "reactive," and the remaining 15 were "nonreactive." The dose of histamine producing a 35% fall in specific airways conductance was labeled as ED 35 SGaw. The animals were then sacrificed, and the following biochemical measurements were carried out: intracellular free calcium ion concentrations [Ca 2ϩ ] i in leukocytes and isolated tracheal smooth muscle cells, activities of Na ] i is an important determinant of airway reactivity. Intracellular calcium levels modulate airway response to histamine with higher levels being associated with greater reactivity. [Japanese Journal of Physiology, 51, 577-583, 2001] Relationship between Intracellular Calcium and Airway Reactivity in Guinea Pigs ] i , intracellular free calcium concentration; SGaw, specific airway conductance; ED 35 histamine, dose of histamine that produced a fall of 35% in SGaw; LPC, lysophosphatidylcholine.

Transient receptor potential and other ion channels as pharmaceutical targets in airway smooth muscle cells

“…Several studies have highlighted differences in the activities of various ion channels and other signalling components in ASM cells in the normal and diseased states. When compared to cells from normal (non‐hyperresponsive) rats and guinea pigs, ASM cells isolated from hyperresponsive animals showed a positive correlation between (i) the amount of Ca 2+ released from intracellular stores and/or the rate of Ca 2+ influx and (ii) the degree of cell contraction 21–23 . An increase in [Ca 2+ ] cyt has been proposed to serve as a common pathway that mediates ASM hyperplasia, increased force of ASM contraction, and the cellular effects of various inflammatory mediators (e.g.…”