EFFECTS OF VARIOUS PHARMACOLOGICAL AGENTS ON ISOLATED HUMAN BRONCHIAL AND PULMONARY ARTERIAL AND VENOUS MUSCLE PREPARATIONS CONTRACTED BY LEUKOTRIENE D₄

Abstract

The response of isolated human bronchial muscle preparations to leukotriene D4 (LTD4, 0.1 microM; 0.22 +/- 0.03 g/mm2) was similar to that of histamine (50 microM; 0.21 +/- 0.02 g/mm2). Isolated pulmonary venous preparations also contracted to these same concentrations of both agonists (LTD4, 0.32 +/- 0.19 g/mm2; and histamine, 0.36 +/- 0.07 g/mm2). However, pulmonary arterial preparations responded to histamine (50 microM, 0.59 +/- 0.10 g/mm2) but exhibited a reduced response to LTD4 (0.3 microM, 0.06 +/- 0.01 g/mm2). Bronchial and pulmonary venous muscle preparations from the human lung had the same sensitivities to LTD4 (pD2 values: bronchus, 7.95 +/- 0.08 and vein, 7.76 +/- 0.07). When bronchial or pulmonary venous muscle preparations were incubated for 30 min with either diltiazem (10 microM), indomethacin (1.7 microM) or L-cysteine (3 microM), the LTD4 cumulative concentration-effect curves following these drug treatments were similar to controls. However, FPL-55712 (10 microM) significantly shifted the LTD4 concentration-effect curves produced in bronchial preparations to the right. In isolated pulmonary arterial preparations none of these drug treatments enhanced the LTD4 response. These results show that isolated human pulmonary arterial preparations are less responsive to LTD4 than bronchial or venous preparations. In addition, the data obtained subsequent to the various drug treatments indirectly suggest that the LTD4 contraction is not modified by a calcium channel blocker or by inhibition of the endogenous products of the cyclooxygenase pathway.

Pharmacological evidence for a novel cysteinyl‐leukotriene receptor subtype in human pulmonary artery smooth muscle

“…Previous reports (Hanna et al ., 1981; Schellenberg & Foster, 1984; Bourdillat et al ., 1987) have demonstrated that human isolated pulmonary arteries exhibited only a small response when stimulated by cysLTs. These observations were recently confirmed by Bäck et al .…”

International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors

“…times more potent. The data reported indicate that the agonist potencies for relaxation of human vascular preparations (pEC 50 values, approximately, 11-10) (Allen et al, 1992;Ortiz et al, 1995) are markedly different from the potencies required to produce contractions in the same tissue (pEC 50 values, approximately, 9 -7) (Schellenberg and Foster, 1984;Bourdillat et al, 1987;Allen et al, 1992;Labat et al, 1992;Ortiz et al, 1995;StankeLabesque et al, 2000). Such data suggest that either the receptors on the endothelium associated with the relaxation are different from the receptors responsible for the contraction or the G-protein second messengers may be coupled more efficiently.…”

“…Collectively, the results with these chemically distinct antagonists (Table 5) provided pertinent pharmacological support for the presence of two receptors in the various tissue preparations. Hanna et al (1981) reported that cys-LTs contracted not only isolated human airways but also human pulmonary veins and noted that the maximum responses on human pulmonary arteries were small (Schellenberg and Foster, 1984;Bourdillat et al, 1987). Berkowitz et al (1984) studied vascular preparations from several species (rat, rabbit, and guinea pig) and observed small contractions in guinea pig pulmonary veins, the inferior vena cava and jugular vein; the effects of LTC 4 were not examined.…”

Leukotriene receptors on human pulmonary vascular endothelium

“…A considerable amount of evidence has been published demonstrating the contractile effects of leukotrienes (LT) in a variety of smooth muscle preparations from several animal species including man (Dahlen et al, 1980;Hanna et al, 1981;Buckner et al, 1986;Bourdillat et al, 1987). However, LT are also known to produce endothelium-dependent relaxations in vessels from different species (Burke et al, 1982;Secrest et al, 1985;Sakuma & Levi, 1988).…”