DOI: 10.1111/j.1748-1716.1983.tb07289.x. Mechanisms of leukotriene‐induced contractions of guinea pig airways: Leukotriene C<sub>4</sub> has a potent direct action whereas leukotriene B<sub>4</sub> acts indirectly

Mechanisms of leukotriene‐induced contractions of guinea pig airways: Leukotriene C4 has a potent direct action whereas leukotriene B4 acts indirectly

10.1111/j.1748-1716.1983.tb07289.x

Crossref journal-article

Wiley

Acta Physiologica Scandinavica (311)

Abstract

The leukotrienes (LT's) are a group of arachidonic acid derivatives implicated as mediators of allergic bronchoconstriction and acute inflammation. Tracheal spirals and strips of lung parenchyma from guinea pigs were used under non‐flow conditions to characterize the contractions caused by LTA4, LTB4 and LTC4. Cumulative administrations of leukotrienes desensitized the lung strip, whereas non‐cumulative dose‐response relationships for the leukotrienes and histamine were reasonably parallel. Half maximal contractions of the lung strips were obtained at a final bath concentration of 1 nM for LTC4 and 300 nM for LTA4 or LTB4, as compared with 6000 nM for histamine. In the trachea, LTC4 was approximately 100 times more potent than LTA4 and histamine. Leukotrienes B4 and C4, but not acetylcholine or histamine, elicited release of the bronchoconstrictive thromboxane A2 from the lung under non‐flow conditions. Indomethacin blocked the contractile response to LTB4, whereas the contractile effect of LTC4 remained unaltered. The β‐adrenoceptor agonist isoproterenol and the LTC4 antagonist FPL 55712 attenuated the contraction, but not the release of thromboxane A2, induced by LTC4. Changing to a perifusion technique rendered the lung strips less sensitive to the direct action of LTC4, and released thromboxane A2 now contributed significantly to the contractile response. In addition, the perifusion experiments indicated that LTB4 released histamine as well. We conclude that the chemoattractant LTB4 is an indirectly acting bronchoconstrictor, whereas the slow reacting substance LTC4 contracts the airway muscle by a predominantly direct mechanism. The exquisite bronchoconstrictive activity of LTC4 may be unrelated to its ability to induce formation of thromboxane A2.

Bibliography

DAHLÃN, S., HEDQVIST, P., WESTLUND, P., GRANSTRÃM, E., HAMMARSTRÃM, S., LINDGREN, J. Ã., & RÃDMARK, O. (1983). Mechanisms of leukotrieneâinduced contractions of guinea pig airways: Leukotriene C4 has a potent direct action whereas leukotriene B4 acts indirectly. Acta Physiologica Scandinavica, 118(4), 393â403. Portico.

Authors 7

SVEN‐ERIK DAHLÉN (first)
PER HEDQVIST (additional)
PÄR WESTLUND (additional)
ELISABETH GRANSTRÖM (additional)
SVEN HAMMARSTRÖM (additional)
JAN ÅKE LINDGREN (additional)
OLOF RÅDMARK (additional)

References 31 Referenced 70

10.1016/0090-6980(82)90015-6
10.1038/newbio245215a0 / Nature New biol / Selective inhibitor of slow reacting substance of anaphylaxis by AUGSTEIN J. (1973)
{'key': 'e_1_2_1_3_1', 'first-page': '1', 'volume-title': 'Advances in prostaglandin, thromboxane and leukotriene research', 'author': 'BJÖRK J.', 'year': '1983'} / Advances in prostaglandin, thromboxane and leukotriene research by BJÖRK J. (1983)
10.1152/physrev.1979.59.3.606
10.1016/0014-2999(82)90318-1
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10.1126/science.7063880

Dates

Type	When
Created	16 years, 8 months ago (Dec. 9, 2008, 10:40 a.m.)
Deposited	1 year, 10 months ago (Oct. 18, 2023, 11:48 p.m.)
Indexed	1 year, 7 months ago (Jan. 14, 2024, 6:24 p.m.)
Issued	42 years, 1 month ago (Aug. 1, 1983)
Published	42 years, 1 month ago (Aug. 1, 1983)
Published Online	16 years, 8 months ago (Dec. 8, 2008)
Published Print	42 years, 1 month ago (Aug. 1, 1983)

Funders 0

None

BibTeX

@article{DAHL_N_1983, title={Mechanisms of leukotriene‐induced contractions of guinea pig airways: Leukotriene C4 has a potent direct action whereas leukotriene B4 acts indirectly}, volume={118}, ISSN={1365-201X}, url={http://dx.doi.org/10.1111/j.1748-1716.1983.tb07289.x}, DOI={10.1111/j.1748-1716.1983.tb07289.x}, number={4}, journal={Acta Physiologica Scandinavica}, publisher={Wiley}, author={DAHLÉN, SVEN‐ERIK and HEDQVIST, PER and WESTLUND, PÄR and GRANSTRÖM, ELISABETH and HAMMARSTRÖM, SVEN and LINDGREN, JAN ÅKE and RÅDMARK, OLOF}, year={1983}, month=aug, pages={393–403} }

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