Effects of bradykinin on intracellular calcium regulation in human ciliated airway epithelium.
The Ca(2+)-mobilizing action of bradykinin (BK) was investigated in ciliated human nasal epithelial (HNE) cells utilizing fura-2 fluorescence and microspectrofluorimetry. In ciliated cells, basal intracellular Ca2+ concentration ([Ca2+]i) was 123 +/- 3 nM (n = 142). BK caused [Ca2+]i to increase (spike) rapidly (within 6 s) to greater than 550 nM by releasing Ca2+ from intracellular pools. The mean effective dose for the process was 1.5 x 10(-7) M BK. The spike was due to the activation of a beta 2-receptor. The spike was unaffected by inhibitors of either cyclooxygenase or voltagegated Ca2+ channels. After the spike, [Ca2+]i decreased to a plateau level (120-250 nM). This plateau persisted (up to 10 min) until the addition of La3+ (0.3 x 10(-3) M) or until the removal of either extracellular Ca2+ or the agonist. No changes in adenosine 3',5'-cyclic monophosphate (cAMP) levels were detected after BK exposure. Additional studies revealed that indomethacin (10(-6) M), isoproterenol (10(-5) M), forskolin (10(-5) M), and dibutyryl cAMP (1 mM) had no effect on [Ca2+]i in ciliated HNE cells. In summary, these data suggest that 1) BK mediates both Ca2+ release from internal pools and Ca2+ entry into the cytoplasm from the extracellular space, and 2) unlike the response to cultured dog airway epithelia, the release of [Ca2+]i in response to BK does not appear to be mediated by either cyclooxygenase pathway or adenylate cyclase-cAMP systems.
Paradiso
A M
AM
Department of Medicine, University of North Carolina, Chapel Hill 27599.
Cheng
E H
EH
Boucher
R C
RC
D000328:Adult; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002923:Cilia; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism*; D009994:Osmolar Concentration
D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D007545:Isoproterenol; D001920:Bradykinin; D002118:Calcium; D007213:Indomethacin