Enhanced calcium signaling to bradykinin in airway smooth muscle from hyperresponsive inbred rats.
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 Ca(2+) 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 Ca(2+) 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 Ca(2+) transients in Fischer than in Lewis ASM cells. ASM cell B(2) receptor expression was similar between the two strains. BK activated both phosphatidylinositide-specific phospholipase C (PI-PLC) and phosphatidylcholine-specific PLC to mobilize Ca(2+) 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 Ca(2+) transients in Fischer cells, whereas GF109203X potentiated while Go6976 and Go6983 did not affect Ca(2+) transients in Lewis cells. Enhanced Ca(2+) mobilization in ASM cells can arise from variations in PKC and may be an important component of nonspecific, innate AHR.
Tao
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FC
Meakins-Christie Laboratories, McGill University, 3626 St. Urbain Street, Montreal, Quebec, Canada H2X 2P2.
Shah
S
S
Pradhan
A A
AA
Tolloczko
B
B
Martin
J G
JG
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344 / Q000502:physiology; D011917:Rats, Inbred Lew; D013997:Time Factors; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology*; D014133:Tracheal Diseases / Q000503:physiopathology*; D010738:Type C Phospholipases / Q000502:physiology
D007295:Inositol Phosphates; D011493:Protein Kinase C; D010727:Phosphoric Diester Hydrolases; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; C105598:phosphatidylcholine-specific phospholipase C; D001920:Bradykinin; D002118:Calcium