Characterisation of the leukotriene receptor(s) on human isolated lung strips.
Leukotriene (LT) B4, LTC4, LTD4 and LTE4 were tested on human isolated lung strips over a wide concentration range (10(-10)-10(-5) M) in the presence and absence of inhibitors of leukotriene metabolism and a range of pharmacological antagonists. LTB4 was inactive on this tissue either alone or in combination with the other leukotrienes. LTC4, LTD4 and LTE4 produced concentration-related contractions with EC50 values of 1.9 x 10(-8) M (95% confidence limits 0.2 - 4.6), 2.1 x 10(-8) M (1.4 - 3.1) and 5.8 x 10(-7) M (2.2 - 13) respectively. They were approximately 100 times more potent than PGF2 alpha [EC50 6.3 x 10(-6) (2.7 - 14.7)]. The maximal responses produced by LTC4 and LTD4 were approximately 120-150% that produced by PGF2 alpha whereas LTE4 produced a maximal response which was only 80% that of PGF2 alpha. L-serine borate (4.5 x 10(-2) M) and L-cysteine (1 x 10(-2) M), selective inhibitors of gamma-glutamyl transpeptidase and aminopeptidase respectively, the specific enzymes responsible for metabolism of LTC4 and LTD4, had little or no effect on the leukotriene responses. A range of common pharmacological antagonists (scopolamine, mepyramine, methysergide, phenoxybenzamine and propranolol) were inactive against both LTC4 and LTD4, as was indomethacin, suggesting that the leukotrienes were acting directly via a specific leukotriene receptor(s).(ABSTRACT TRUNCATED AT 250 WORDS)
Gardiner
P J
PJ
Miles Laboratories Ltd., Research Department, Bucks, U.K.
Cuthbert
N J
NJ
D002867:Chromones / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology
D002867:Chromones; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin; D013189:SRS-A; C006312:FPL 55712