Studies of receptors and modulatory mechanisms in functional responses to cysteinyl-leukotrienes in smooth muscle.
Cysteinyl-leukotrienes, i.e. leukotriene (LT) C4, D4 and E4, are inflammatory mediators and potent airway- and vasoconstrictors. Two different cysteinyl-leukotriene receptors have been cloned, CysLT1 and CysLT2. This report reviews recent data on CysLT receptor characterisation as well as studies of modulatory mechanisms involved in cysteinyl-leukotriene-induced responses. On the basis of functional studies in isolated smooth muscle preparations, the existence of an additional receptor for cysteinyl-leukotrienes is suggested. In addition, cysteinyl-leukotriene responses in pulmonary vessels were regulated by the release of modulatory factors, of which cyclooxygenase products dominated in the arteries and nitric oxide was the main modulator in porcine pulmonary veins. Moreover, the interconversion between LTC4 and LTD4 and the metabolism into LTE4 may represent a major modulatory mechanism in the guinea-pig trachea by deciding which CysLT receptor is activated by the cysteinyl-leukotrienes.
Bäck
Magnus
M
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Magnus.Back@imm.ki.se
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D006973:Hypertension; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D017997:Leukotriene C4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000378:metabolism / Q000494:pharmacology*; D017999:Leukotriene E4 / Q000378:metabolism / Q000494:pharmacology*; D008565:Membrane Proteins; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D011667:Pulmonary Veins / Q000187:drug effects; D018077:Receptors, Leukotriene / Q000819:agonists / Q000145:classification / Q000378:metabolism*; D013552:Swine; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D011453:Prostaglandins; D018077:Receptors, Leukotriene; D017997:Leukotriene C4; D009569:Nitric Oxide; D017998:Leukotriene D4; D017999:Leukotriene E4; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor