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Abstract

Leukotriene C4 binds to receptors and has positive inotropic effects in bullfrog heart.

M Chiono, R S Heller, J J Andazola and C A Herman
Journal of Pharmacology and Experimental Therapeutics March 1991, 256 (3) 1042-1048;
M Chiono
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R S Heller
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J J Andazola
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C A Herman
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Abstract

Leukotriene (LT) C4, LTD4 and LTE4 have positive inotropic effects on contractility of the isolated perfused bullfrog heart. The effects of LTD4 and LTE4 but not LTC4 can be blocked by the mammalian antagonist L-649,923. Characterization of specific binding sites for [3H]LTC4 on membrane preparations from American bullfrog (Rana catesbeiana) ventricle was carried out. Binding assays were done in the presence of serine (5 mM) and borate (10 mM) for 30 min at 23 degrees C. Under these conditions, no metabolism of LTC4 to LTD4 occurred. Specific binding of [3H]LTC4 reached steady state within 10 min, remained constant for 60 min, and was reversible with the addition of 1000-fold excess unlabeled LTC4. Scatchard analysis of the binding data indicated a single class of binding sites with a Kd of 33.9 nM and maximal binding capacity of 51.6 pmol/mg of protein. Competition binding studies revealed an order of potency of LTC4 greater than LTD4 greater than LTE4 with Ki values of 47, 11766 and 32248 nM, respectively. Glutathione and hematin had Ki values of 50566 and 6014 nM, respectively, suggesting that the LTC4 receptor is not a site on glutathione transferase. Two mammalian LTD4 antagonists, L-649,923 and LY171883 failed to inhibit specific binding of [3H]LTC4, suggesting that the LTC4 receptor is distinct from the LTD4 receptor. Guanosine-5'-O-3-thiotriphosphate did not affect specific binding of [3H]LTC4 indicating that, like mammalian LTC4 receptors, a Gi protein is not involved in the transduction mechanism. LTC4 acts on bullfrog hearts through specific membrane receptors and is similar to its mammalian counterpart.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 256, Issue 3
1 Mar 1991
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Abstract

Leukotriene C4 binds to receptors and has positive inotropic effects in bullfrog heart.

M Chiono, R S Heller, J J Andazola and C A Herman
Journal of Pharmacology and Experimental Therapeutics March 1, 1991, 256 (3) 1042-1048;

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Abstract

Leukotriene C4 binds to receptors and has positive inotropic effects in bullfrog heart.

M Chiono, R S Heller, J J Andazola and C A Herman
Journal of Pharmacology and Experimental Therapeutics March 1, 1991, 256 (3) 1042-1048;
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