Leukotriene C4 inhibits ciliary activity in the presence of gamma-glutamyl transpeptidase.
We incubated human paranasal sinus mucosa in tissue culture with each of leukotrienes C4, D4, and E4 (LTC4, LTD4, and LTE4). Ciliary beat frequency (CBF) was measured photoelectrically, and the concentrations of leukotrienes in the incubation medium were determined over time. LTC4 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, LTC4 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. LTD4 also exhibited progressive ciliary inhibition, while LTE4 had a minimal effect on CBF. In the medium, LTC4 was changed to LTD4 and further to LTE4. gamma-Glutamyl transpeptidase (gamma-GTP), an enzyme that converts LTC4 to LTD4, was detected in the mucosa. Serine-borate complex, an inhibitor of gamma-GTP, blocked the inhibitory effect of LTC4 on CBF. These findings suggest that LTC4 may induce ciliary inhibition indirectly by conversion to LTD4.
Ganbo
T
T
Division of Otopathology, University of Pittsburgh, Pennsylvania 15213, USA.
Hisamatsu
K
K
Inoue
H
H
D001881:Borates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000494:pharmacology; D017999:Leukotriene E4 / Q000494:pharmacology; D009079:Mucociliary Clearance / Q000187:drug effects*; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology; D010256:Paranasal Sinuses / Q000187:drug effects / Q000502:physiology; D012694:Serine / Q000494:pharmacology; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000494:pharmacology*
D001881:Borates; C040900:serine-borate complex; D017997:Leukotriene C4; D012694:Serine; D017998:Leukotriene D4; D017999:Leukotriene E4; D005723:gamma-Glutamyltransferase