Leukotriene C4 inhibits ciliary activity in the presence of gamma-glutamyl transpeptidase
Ganbo, T.; Hisamatsu, K.; Inoue, H.
American Journal of Physiology 271(2 Pt 1): L216-L224
1996
ISSN/ISBN: 0002-9513 PMID: 8770059 Document Number: 467720
We incubated human paranasal sinus mucosa in tissue culture with each of leukotrienes C-4, D-4, and E-4 (LTC-4, LTD-4, and LTE-4). Ciliary beat frequency (CBF) was measured photoelectrically, and the concentrations of leukotrienes in the incubation medium were determined over time. LTC-4 significantly decreased CBF with 2-h, 4-h, and 8-h exposures to 10-6 M, 10-8 M, and 10-10 M, respectively. Moreover, LTC-4 dose dependently reduced CBF to 81.4% of the initial value after 6-h exposure to 10-6 M, to 82.5% after 8-h exposure to 10-8 M, and to 89.7% after 12-h exposure to 10-10 M. LTD-4 also exhibited progressive ciliary inhibition, while LTE-4 had a minimal effect on CBF. In the medium, LTC-4 was changed to LTD-4 and further to LTE-4. gamma-Glutamyl transpeptidase (gamma-GTP), an enzyme that converts LTC-4 to LTD-4, was detected in the mucosa. Serine-borate complex, an inhibitor of gamma-GTP, blocked the inhibitory effect of LTC-4 on CBF. These findings suggest that LTC-4 may induce ciliary inhibition indirectly by conversion to LTD-4.