Evidence for high and low affinity leukotriene D4 receptors mediating vascular responses in the conscious rat.
Leukotriene D4 (0.17-17 nmol/kg i.v.) produced a dose-dependent increase in blood pressure in the conscious rat. Infusion of the selective peptidoleukotriene receptor antagonist, SK&F 104353, produced dose-dependent shifts in the leukotriene D4 dose-response curve. However, SK&F 104353 at doses of 0.2 mg/kg + 1 mg/kg per h or 1 mg/kg + 3 mg/kg per h produced similar dose ratios of 9.2 +/- 1.1 and 9.2 +/- 1.6, respectively. The peptidoleukotriene receptor antagonist, ICI 198615, also shifted the LTD4 dose-response curve, although doses of 0.2 mg/kg + 1 mg/kg per h, 1 mg/kg + 3 mg/kg per h or 2 mg/kg + 10 mg/kg per h produced similar dose ratios of 15.7 +/- 3.4, 19.1 +/- 6.3 and 16.2 +/- 3.6, respectively. The similarity in the dose ratios observed despite increasing doses of either SK&F 104353 or ICI 198615 suggests the existence of two vascular leukotriene D4 receptor subpopulations, differentiated by high and low agonist affinity.
Smith
E F
EF
Smith Kline & French Laboratories, Department of Pharmacology, King of Prussia, PA 19406.
Slivjak
M J
MJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003998:Dicarboxylic Acids / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000502:physiology*; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D003998:Dicarboxylic Acids; D007191:Indazoles; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A; C054217:ICI 198615; C052393:pobilukast