An examination of the ability of d-tubocurarine to evoke contraction and mediator release from superfused trachea and parenchymal strips isolated from the guinea pig

RI Fishleder, J Ro, FM Graziano, JA Will and CK Buckner

The relationship between curare-induced mediator release and contraction in superfused guinea pig trachea and parenchymal strips was examined. In trachea, curare produced histamine release and contraction with peak release occurring in the first 90 sec (collection period 1) after challenge. Peak contraction developed later (collection periods 4- 6). Curare-induced contraction of parenchymal strips was inconsistent and smaller than that found in trachea. No histamine could be detected in parenchymal strip superfusate samples. Curare also was selective in releasing histamine from monodispersed airway cells vs. peripheral lung cells. No leukotriene bioactivity or immunoreactivity could be detected after curare challenge of tissues or cell suspensions. Tracheal contractions, but not histamine release, occurring early (first 5 or 6 collection periods) after challenge were antagonized by mepyramine, 10(- 6) M, and phenoxybenzamine, 3 X 10(-5) M. Combination of FPL55712, 10(- 5) M, with mepyramine did not further alter tracheal contraction. Contractions occurring later after challenge and total histamine release were enhanced by indomethacin, 5 X 10(-6) M. Indomethacin also increased contractions in the presence of mepyramine. With mepyramine and indomethacin, LY171883, 1 and 3 X 10(-6) M, and nordihydroguaiaretic acid, 3 X 10(-5) M, antagonized tracheal contractions to curare, 3 X 10(-3) M, but not to 1 X 10(-3) M, without altering histamine release. Indomethacin prolonged return to base line of tracheal tension after challenge with exogenous histamine. After addition of LY171883 or nordihydroguaiaretic acid, the return of tracheal tension after histamine was not different from that seen without drug pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 242, Issue 2, pp. 558-565, 08/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics