To determine the distribution of leukotriene (LT) C4 and LTD4 receptors and functional significance of each receptor, we used [3H]LTC4 and [3H]LTD4 to measure the binding activity in various tissue homogenates and to correlate the relative ability of the LT agonists to inhibit binding and their contractile responses in guinea-pig uterine or lung parencymal preparations. Guinea-pig brain contained the highest binding activity of 1 to 2 nM [3H]LTC4 followed by small intestine, heart, lung, kidney, uterus, etc., whereas guinea-pig lung had at least 2.7-fold greater [3H]LTD4 binding activity than any other tissues tested. In the brain and uterine homogenates, the rank order of potency for the compounds in competing with [3H]LTC4 for binding sites was LTC4 >> LTD4 > LTE4 > FPL-55712 = arachidonic acid. The in vitro functional study showed that the ability of the LT agonists to produce uterine contraction was in the order of LTC4 > LTD4 > LTE4, which is compatible with their relative effect for inhibition of uterine or brain [3H]LTC4 binding. In the lung homogenate, either LTC4, LTD4 or LTE4 inhibited effectively [3H]LTD4 binding and the potency order for the [3H]LTD4 competition study was LTD4 > LTE4 > LTC4 >> FPL-55712 > arachidonic acid. These LT agonists also produced lung contraction effectively and the difference among their contractile ability was not significant. We conclude that 1) there are distinct functional LTC4 and LTD4 receptors, 2) activation of the LTC4 receptor could account for the uterine contraction due to the LT agonists and 3) the lung contraction induced by LTC4, LTD4 and LTE4 is at least mediated partly by the LTD4 receptor.
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - 1985|
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