Receptor preferences of cysteinyl-leukotrienes in the guinea pig lung parenchyma.
Two cysteinyl-leukotriene receptors, CysLT(1) and CysLT(2) receptors, have been cloned, but the contractions to cysteinyl-leukotrienes in the guinea pig lung parenchyma have been reported to be resistant to CysLT(2) receptor antagonism and to be only partially inhibited by CysLT(1) receptor antagonism. The receptor preferences of the individual cysteinyl-leukotrienes (leukotriene C(4), D(4) and E(4)) in the guinea pig lung parenchyma were studied in organ baths. CysLT(1) receptor antagonists competitively inhibited the contraction to leukotriene E(4), but exhibited only weak antagonism of contractions to leukotriene C(4) and D(4). In the presence of the cyclooxygenese inhibitor indomethacin and the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NOARG), the CysLT(1) receptor antagonists did not further inhibit the leukotriene D(4)-induced contraction. These results suggest that leukotriene E(4) solely activates a CysLT(1) receptor, and that the CysLT(1) receptor antagonist-resistant contraction to leukotriene D(4) and C(4) is mediated via another CysLT receptor.
Sakata
Kiyoto
K
Experimental Asthma and Allergy Research, Institute of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Bäck
Magnus
M
D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000494:pharmacology; D017997:Leukotriene C4 / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000494:pharmacology*; D017999:Leukotriene E4 / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins; D009119:Muscle Contraction / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D048448:Phenylcarbamates; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D018077:Receptors, Leukotriene / Q000502:physiology; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000494:pharmacology
D001993:Bronchodilator Agents; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007211:Indoles; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D048448:Phenylcarbamates; D011422:Propionates; D011804:Quinolines; D018077:Receptors, Leukotriene; D013449:Sulfonamides; D014105:Tosyl Compounds; D019335:Nitroarginine; D017997:Leukotriene C4; C059141:verlukast; D017998:Leukotriene D4; D017999:Leukotriene E4; C412375:cysteinyl leukotriene receptor 2; D019001:Nitric Oxide Synthase; C083169:leukotriene D4 receptor; D007213:Indomethacin; C062735:zafirlukast