1 Experimental Asthma and Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden
Correspondence to: Experimental Asthma & Allergy Research, The National Institute of Environmental Medicine, Box 287, SE-171 77 Stochkolm, Sweden. E-mail: Magnus.Back@imm.ki.se
1 Leukotriene B4 (LTB4) is a potent leukocyte chemoattractant, acting on specific receptors, BLT receptors. The aim of this study was to examine the mechanism of action of LTB4 in the guinea-pig lung, using strips of lung parenchyma (GPLP), spirals of trachea (GPT) and bronchus (GPB) and rings of pulmonary artery (GPPA). Mechanical responses were studied in organ baths, and mediator release was assessed using enzyme immuno assay.
2 LTB4 induced similar contractions of GPLP and GPPA, whereas LTB4 had only small contractile effects in GPT and GPB. In addition, the contractile response to LTB4 was reproduced in the human pulmonary artery.
3 In the GPLP, the unselective BLT receptor antagonist ONO-4057 abolished the contractions induced by LTB4, whereas the selective BLT1 receptor antagonist U–75302 only partly inhibited the LTB4-induced contractions. In the GPPA, both antagonists abolished the response to LTB4.
4 The effect of LTB4 in GPPA and GPLP was indirect and mediated by the release of thromboxane A2 and histamine, as supported by selective pharmacologic interventions and measurements of thromboxane B2 and histamine in the organ baths.
5 In conclusion, the results indicate a new biological function of LTB4, namely to constrict isolated pulmonary arteries. Moreover, the findings suggest that the LTB4-induced contractions of GPPA were mediated by a BLT1 receptor, whereas BLT2 receptor activation accounted for a major part of the contraction of GPLP, making the latter preparation a suitable assay for BLT2 receptors.
British Journal of Pharmacology (2004) 141, 449–456. doi:10.1038/sj.bjp.0705641
Keywords: Leukotriene B4; guinea-pig lung parenchyma; pulmonary artery; vasoconstriction; BLT receptor; histamine; thromboxane A2
Abbreviations: AUC, area under the curve; GPB, guinea-pig bronchus; GPLP, guinea-pig lung parenchyma; GPPA, guinea-pig pulmonary artery; GPT, guinea-pig trachea; HPA, human pulmonary artery; LTB4, leukotriene B4; TXA2, thromboxane A2; TXB2, thromboxane B2
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