The present study was carried out to examine the relationship between intra
cellular free calcium ion concentrations and its regulatory enzymes, sodium
potassium adenosine triphosphatase (Na+,K+-ATPase) and calcium adenosine t
riphosphatase (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 wit
h a greater than 35% fall in specific airways conductance and were labeled
as "reactive," and the remaining 15 were "nonreactive." The dose of histami
ne producing a 35% fall in specific airways conductance was labeled as ED35
SGaw. The animals were then sacrificed, and the following biochemical meas
urements were carried out: intracellular free calcium ion concentrations [C
a2+](i) in leukocytes and isolated tracheal smooth muscle cells, activities
of Na+,K+-ATPase and Ca2+- ATPase in tracheal homogenate, and plasma level
s of lysophosphatidy/choline (LPC). Reactive guinea pigs showed significant
ly higher [Ca2+](i) and Na+,K+-ATPase and Ca2+-ATPase activities. Airway re
activity (ED35 SGaw) had significant negative correlation with [Ca2+](i), w
ith activities of each of the ATPases and with plasma lysophosphatidylcholi
ne. It is concluded that the level of [Ca2+](i) is an important determinant
of airway reactivity. Intracellular calcium levels modulate airway respons
e to histamine with higher levels being associated with greater reactivity.