Abstract

Leukotrienes (LT) are potent spasmogenic agents in human isolated bronchial and pulmonary venous muscle preparations. Treatment of human isolated pulmonary veins with the L-serine borate complex (45 mM; 30 min) did not alter the LTC4 pD2 values in these preparations. The cysteinyl LT antagonists, ICI 198615, MK 571 and SKF 104353, significantly shifted to the right the LT concentration-effect curves in airways with pKB values against LTC4 of 8.4 for ICI 198615, 8.6 for MK 571 and 8.0 for SKF 104353. Similar results were found against LTD4. In contrast, these antagonists did not inhibit the LTC4 and LTD4 contractions in human pulmonary veins. LTE4 was a partial agonist on the human pulmonary veins and blocked the contractions with a pKp value of 6.3 against LTD4 and 6.6 against LTC4. An LT analog, BAY u9773, also blocked the LT contractions in bronchial and venous muscle preparations with pKp values against LTD4 and LTC4 of 6.5 and 6.7, respectively. These data provide pharmacological evidence for a second cysteinyl LT receptor in the human lung. One LT receptor (LT-1) is stimulated by all cysteinyl LT, found on airways and inhibited by the LT-1 antagonists, and a second receptor (LT-2) can also be stimulated by all cysteinyl LT and is found on pulmonary veins, resistant to LT-1 antagonists but blocked by LTE4 and the dual LT-1/LT-2 antagonist BAY u9773.