Relationship between intracellular calcium and airway reactivity in guinea pigs

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⁺,K⁺-ATPase) and calcium adenosine triphosphatase (Ca²⁺-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 ED₃₅ SGaw. The animals were then sacrificed, and the following biochemical measurements were carried out: intracellular free calcium ion concentrations [Ca²⁺]_i in leukocytes and isolated tracheal smooth muscle cells, activities of Na⁺,K⁺-ATPase and Ca²⁺-ATPase in tracheal homogenate, and plasma levels of lysophosphatidylcholine (LPC). Reactive guinea pigs showed significantly higher [Ca²⁺]_i and Na⁺,K⁺-ATPase and Ca²⁺-ATPase activities. Airway reactivity (ED₃₅ SGaw) had significant negative correlation with [Ca²⁺]_i, with activities of each of the ATPases and with plasma lysophosphatidylcholine. It is concluded that the level of [Ca²⁺]_i is an important determinant of airway reactivity. Intracellular calcium levels modulate airway response to histamine with higher levels being associated with greater reactivity.