Journal of Applied Physiology, Vol 58, Issue 3 859-868, Copyright © 1985 by American Physiological Society
Endogenous prostaglandins modulate histamine-induced contraction in canine tracheal smooth muscle
S. A. Shore, W. S. Powell and J. G. Martin
We studied the role of endogenous prostaglandins in modulating the
histamine response of canine tracheal smooth muscle (TSM) in vitro.
Indomethacin (INDO) (10(-7) - 10(-5) M), a cyclooxygenase and prostaglandin
synthesis inhibitor, significantly increased maximum histamine-induced
tension (Tmax) and decreased the concentration of histamine required to
produce 50% of Tmax (EC50). Acetylsalicylic acid (10(-5) -5 X 10(-4) M),
another less potent cyclooxygenase inhibitor, also decreased EC50. Neither
the lipoxygenase inhibitor nordihydroguaiaretic acid nor the leukotriene
antagonist FPL 55712 had any effect on histamine-induced tension in
INDO-pretreated TSM. INDO reduced the standard deviation of EC50 from 0.47
in control TSM (n = 51) to 0.26 in INDO-pretreated TSM (n = 31) (P less
than 0.02). High-pressure liquid chromatography established prostacyclin
(PGI2), through its degradation product 6-oxo-PGF1 alpha, as the
predominant prostaglandin produced by canine TSM. Exogenous PGI2 caused a
concentration-dependent relaxation of histamine-contracted TSM. In the
tissue bath, spontaneous efflux of 6-oxo-PGF1 alpha from TSM, as measured
by radioimmunoassay, averaged 4.7 ng . g muscle-1 . min-1 and increased to
10 ng/g muscle (n = 10, P less than 0.001) with administration of
histamine. The isometric tension produced by histamine (10(-4) M) was
inversely linearly correlated with the log concentration of endogenous
6-oxo-PGF1 alpha (r = 0.81, P less than 0.01). Our results are consistent
with an important role for endogenous bronchodilating prostaglandins,
probably prostacyclin, in determining both the histamine sensitivity of
canine TSM in vitro and its variability among individual animals.
