Journal of Applied Physiology, Vol 63, Issue 6 2450-2459, Copyright © 1987 by American Physiological Society
A formyl peptide contracts guinea pig lung: role of arachidonic acid metabolites
S. A. Shore, N. P. Stimler-Gerard, E. Smith and J. M. Drazen
Department of Medicine, Beth Israel Hospital, Boston, Massachusetts.
We studied the role of cyclooxygenase and lipoxygenase products of
arachidonic acid metabolism in mediating
N-formyl-methionyl-leucyl-phenylalanine- (FMLP) induced contractions of
guinea pig lung parenchymal strips. The cyclooxygenase inhibitors
indomethacin (10(-5) M) and aspirin (3 X 10(-5) to 10(-4) M), the
lipoxygenase inhibitor nordihydroguaiaretic acid (10(-5) to 3 X 10(-5) M),
and the combined cyclooxygenase/lipoxygenase inhibitors
1-phenyl-3-pyrazolidinone (Phenidone) (3 X 10(-5) to 3 X 10(-4) M) and BW
755C (10(-5) to 10(-4) M) each caused a decrease in the maximum force
induced by FMLP (Fmax) and an increase in the concentration of FMLP
required to produce 50% of Fmax (EC50). The thromboxane synthesis inhibitor
imidazole (3 X 10(-3) M) also decreased Fmax. The leukotriene D4 receptor
antagonist FPL 55712 (5.7 X 10(-6) to 1.9 X 10(-5) M) increased the EC50
for FMLP, whereas desensitization of lung parenchymal strips to leukotriene
B4 by pretreatment with this leukotriene (10(-7) M) had no effect on
FMLP-induced contraction. After exposure to FMLP (10(-6) M), guinea pig
lung produced (as determined by high-performance liquid chromatography and
radioimmunoassay) leukotrienes C4 and B4, thromboxane A2 (as measured by
its stable degradation product thromboxane B2), and prostaglandin F2 alpha.
Lung strips not exposed to FMLP showed no evidence of leukotriene
production. We conclude that thromboxane A2 and leukotriene C4 generated in
response to FMLP mediate a substantial fraction of the force induced by
this peptide in guinea pig lung parenchymal strips.
