Interaction of thromboxane A2 and leukotrienes in guinea pig airways in vivo.
Effects of a thromboxane A2 receptor antagonist (S-1452) on bronchoconstriction induced by inhaled leukotriene C4 and a leukotriene receptor antagonist (AS-35) on bronchoconstriction caused by inhalation of a thromboxane A2 mimetic (STA2) were studied in anesthetized, artificially ventilated guinea pigs in order to examine the interaction of thromboxane A2 and leukotrienes in airways. 0.01-1.0 mu g/ml of leukotriene C4 and 0.1-1.0 mu g/ml of STA 2 inhaled from ultrasonic nebulizer developed for small animals caused dose-dependent increase of pressure at the airway opening (Pao) which is considered to be an index representing bronchial response. Pretreatment of the animals with inhaled S-1452 (0.01, 0.033 mg/ml) significantly reduced the airway responses produced by 0.01,0.033,0.1,0.33 and 1.0 mu g/ml of leukotriene C4 in a dose dependent manner. While pretreatment with inhaled AS-35 (1mg) did not affect the STA2 dose-response curve. These findings suggest that leukotriene C4 activates thromboxane A2 generation while thromboxane A2 does not influence 5-lipoxygenase pathway in the airways.
Fujimura
M
M
Third Department of Internal Medicine, Kanazawa University, School of Medicine, Japan.
Bando
T
T
Mizuhashi
K
K
Matsuda
T
T
D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000139:chemically induced; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D016084:Bronchoconstriction; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011744:Pyrimidinones; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane; D013189:SRS-A / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D011725:Pyridines; D011743:Pyrimidines; D011744:Pyrimidinones; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013189:SRS-A; D013777:Tetrazoles; C073308:AS 35; C056566:S 145; D013928:Thromboxane A2; C037866:STA 2; D006632:Histamine