TY - JOUR
T1 - Enhanced calcium signaling to bradykinin in airway smooth muscle from hyperresponsive inbred rats
AU - Tao, F. C.
AU - Shah, S.
AU - Pradhan, A. A.
AU - Tolloczko, B.
AU - Martin, James G.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Inbred Fischer 344 rats display airway hyperresponsiveness (AHR) in vivo compared with the normoresponsive Lewis strain. Fischer AHR has been linked with increased airway smooth muscle (ASM) contraction ex vivo and enhanced ASM cell intracellular Ca2+ mobilization in response to serotonin compared with Lewis. To determine the generality of this association, we tested whether bradykinin (BK) also stimulates greater contraction of Fischer airways and greater Ca2+ mobilization in Fischer ASM cells. Explants of Fischer intraparenchymal airways constricted faster and to a greater degree in response to BK than Lewis airways. BK also evoked higher Ca2+ transients in Fischer than in Lewis ASM cells. ASM cell B2 receptor expression was similar between the two strains. BK activated both phosphatidylinositide-specific phospholipase C (PI-PLC) and phosphatidylcholine-specific PLC to mobilize Ca2+ in Fischer and Lewis ASM cells. PI-PLC activity, as measured by inositol polyphosphate accumulation, was similar in the two strains. PKC inhibition with GF109203X, Go6973, or Go6983 attenuated BK-mediated Ca2+ transients in Fischer cells, whereas GF109203X potentiated while Go6976 and Go6983 did not affect Ca2+ transients in Lewis cells. Enhanced Ca2+ mobilization in ASM cells can arise from variations in PKC and may be an important component of nonspecific, innate AHR.
AB - Inbred Fischer 344 rats display airway hyperresponsiveness (AHR) in vivo compared with the normoresponsive Lewis strain. Fischer AHR has been linked with increased airway smooth muscle (ASM) contraction ex vivo and enhanced ASM cell intracellular Ca2+ mobilization in response to serotonin compared with Lewis. To determine the generality of this association, we tested whether bradykinin (BK) also stimulates greater contraction of Fischer airways and greater Ca2+ mobilization in Fischer ASM cells. Explants of Fischer intraparenchymal airways constricted faster and to a greater degree in response to BK than Lewis airways. BK also evoked higher Ca2+ transients in Fischer than in Lewis ASM cells. ASM cell B2 receptor expression was similar between the two strains. BK activated both phosphatidylinositide-specific phospholipase C (PI-PLC) and phosphatidylcholine-specific PLC to mobilize Ca2+ in Fischer and Lewis ASM cells. PI-PLC activity, as measured by inositol polyphosphate accumulation, was similar in the two strains. PKC inhibition with GF109203X, Go6973, or Go6983 attenuated BK-mediated Ca2+ transients in Fischer cells, whereas GF109203X potentiated while Go6976 and Go6983 did not affect Ca2+ transients in Lewis cells. Enhanced Ca2+ mobilization in ASM cells can arise from variations in PKC and may be an important component of nonspecific, innate AHR.
KW - Bradykinin
KW - Protein kinase C
UR - http://www.scopus.com/inward/record.url?scp=0037216183&partnerID=8YFLogxK
U2 - 10.1152/ajplung.00023.2002
DO - 10.1152/ajplung.00023.2002
M3 - Article
C2 - 12388355
AN - SCOPUS:0037216183
SN - 0002-9513
VL - 284
SP - L90-L99
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 1 28-1
ER -