Leukotriene D4 potentiates histamine-induced bronchoconstriction in guinea-pigs

1984 ◽  
Vol 15 (3-4) ◽  
pp. 146-152 ◽  
Author(s):  
A. G. Stewart ◽  
D. C. Thompson ◽  
M. R. Fennessy
Keyword(s):  
Guinea Pigs ◽  
Leukotriene D4

Pharmacology of L-660,711 (MK-571): a novel potent and selective leukotriene D4 receptor antagonist

1989 ◽  
Vol 67 (1) ◽  
pp. 17-28 ◽  
Author(s):  
T. R. Jones ◽  
R. Zamboni ◽  
M. Belley ◽  
E. Champion ◽  
L. Charette ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Receptor Antagonist ◽  
Guinea Pigs ◽  
Competitive Inhibitor ◽  
Dose Ratio ◽  
Leukotriene D4 ◽  
Small Component ◽  
Human Trachea ◽  
D4 Receptor ◽  
Orally Active

L-660,711 (3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl) ((3-dimethyl amino-3-oxo propyl)thio)methyl)thio)propanoic acid is a potent and selective competitive inhibitor of [3H]leukotriene D4 binding in guinea pig (Ki value, 0.22 nM) and human (Ki value, 2.1 nM) lung membranes but is essentially inactive versus [3H]leukotriene C4 binding (IC50 value in guinea pig lung, 23 μM). Functionally it competitively antagonized contractions of guinea pig trachea and ileum induced by leukotriene (LT) D4 (respective pA2 values, 9.4 and 10.5) and LTE4 (respective pA2 values, 9.1 and 10.4) and contractions of human trachea induced by LTD4 (pA2 value, 8.5). L-660,711 (5.8 × 10−8 M) antagonized contractions of guinea pig trachea induced by LTC4 in the absence (dose ratio = 28) but not in the presence of 45 mM L-serine borate (dose ratio <2). L-660,711 (1.9 × 10−5 M) did not block contractions of guinea pig trachea induced by histamine, acetylcholine, 5-hydroxytryptamine, PGF2α, U-44069, or PGD2. In the presence of atropine, mepyramine, and indomethacin, L-660,711 (1.9 × 10−5 M) inhibited a small component of the response to antigen on guinea pig trachea but completely blocked anti-IgE-induced contractions of human trachea. L-660,711 (i.v.) antagonized bronchoconstriction induced in anesthetized guinea pigs by i.v. LTC4, LTD4, and LTE4 but did not block bronchoconstriction to arachidonic acid, U-44069, 5-hydroxytryptamine, histamine, or acetylcholine. Intraduodenal L-660,711 antagonized LTD4 (0.2–12.8 μg/kg) -induced bronchoconstriction in guinea pigs, and p. o. L-660,711 blocked LTD4- and Ascaris-induced bronchoconstriction in conscious squirrel monkeys and ovalbumin-induced bronchoconstriction in conscious sensitized rats treated with methysergide (3 μg/kg). The pharmacological profile of L-660,711 indicates that it is a potent, selective, orally active leukotriene receptor antagonist which is well suited to determine the role played by LTD4 and LTE4 in asthma and other pathophysiologic conditions.

Differing mechanisms for leukotriene D4-induced bronchoconstriction in guinea pigs following intravenous and aerosol administration

1982 ◽  
Vol 24 (3) ◽  
pp. 419-432 ◽  
Author(s):  
R. Hamel ◽  
P. Masson ◽  
A.W. Ford-Hutchinson ◽  
T.R. Jones ◽  
G. Brunet ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Leukotriene D4

Effect of combined leukotriene D4 and thromboxane A2 receptor antagonist on mediator-controlled resistance in guinea pigs

2000 ◽  
Vol 403 (1-2) ◽  
pp. 169-179 ◽  
Author(s):  
Yasuhito Arakida ◽  
Keiko Ohga ◽  
Yohei Okada ◽  
Hiroki Morio ◽  
Kiyomi Suwa ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Guinea Pigs ◽  
Thromboxane A2 ◽  
Leukotriene D4 ◽  
Thromboxane A2 Receptor

Different mechanisms between thromboxane A2- and leukotriene D4-induced nasal blockage in guinea pigs

2006 ◽  
Vol 80 (3-4) ◽  
pp. 144-154 ◽  
Author(s):  
Yoshiki Tanaka ◽  
Nobuaki Mizutani ◽  
Masanori Fujii ◽  
Takeshi Nabe ◽  
Shigekatsu Kohno
Keyword(s):  
Guinea Pigs ◽  
Thromboxane A2 ◽  
Leukotriene D4 ◽  
Nasal Blockage

Effect of RG 12525 on pulmonary function in sensitized and non sensitized guinea pigs challenged with leukotriene D4 (LTD4)

1990 ◽  
Vol 183 (2) ◽  
pp. 217
Author(s):  
G.W. Carnathan ◽  
R.G. Van Inwegen ◽  
J.J. Travis ◽  
G.J. Schuessler ◽  
J. Haimovich
Keyword(s):  
Pulmonary Function ◽  
Guinea Pigs ◽  
Leukotriene D4

Effects of timolol, indomethacin, and MK-571 on bronchoconstriction to infused leukotriene D4 in guinea pigs

1990 ◽  
Vol 68 (7) ◽  
pp. 783-790 ◽  
Author(s):  
P. Masson ◽  
T. R. Jones
Keyword(s):  
Receptor Antagonist ◽  
Guinea Pigs ◽  
Dynamic Compliance ◽  
Cyclooxygenase Inhibitor ◽  
Leukotriene D4 ◽  
Duration Of Action ◽  
Adrenoceptor Antagonist ◽  
Lung Resistance ◽  
Leukotriene Receptor ◽  
Delayed Time

Continuous intravenous infusions of leukotriene D4 produced a prolonged but variable bronchoconstriction (approximately a 200% increase in lung resistance (RL) and a 50% decrease in dynamic compliance (Cdyn)) in anesthetized and paralysed guinea pigs that peaked within 1–1.5 min and was followed by a somewhat smaller secondary plateau response. The overall response was delayed (time to peaks) but not significantly reduced by pretreatment with the cyclooxygenase inhibitor indomethacin (1 mg/kg), was markedly potentiated by the β-adrenoceptor antagonist timolol (5 μg/kg), and was partially and completely blocked by pretreatment with 0.1 and 1.0 mg/kg, respectively, of the leukotriene D4 receptor antagonist MK-571. MK-571 prevented the response in indomethacin-treated guinea pigs but was considerably more active at preventing and reversing the potentiated responses (lower dose of leukotriene D4) in animals treated with indomethacin and timolol. Additional studies in indomethacin- and timolol-treated animals demonstrated that MK-571 was active with good duration of action by the aerosol route of administration (30 min and 4 h pretreatment). The technique of infusing leukotrienes into untreated, indomethacin-treated, and indomethacin- and timolol-treated guinea pigs is a useful method to study the action and interaction of leukotriene receptor antagonists.Key words: leukotriene receptor antagonists, cyclooxygenase inhibitor, β-adrenoceptor blockade in guinea pigs, MK-571, L-648,051.

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