Contraction of guinea pig inferior vena cava by eicosanoids.
Guinea pig inferior vena cava contracted in response to leukotriene (LT)C4, LTD4, LTE4 U46619, phenylephrine, histamine, and KCl. Although LTC4, LTD4, and U46619 were the most potent agonists, active tension generated by these eicosanoids was only about half that of histamine or KCl. LTE4 and phenylephrine were marginally active. Biochemical analysis showed vena cava able to convert about 23% LTC4 to LTD4 and LTE4 in 45 min. Pretreatment with acivicin prevented this by abrogating conversion of LTC4 to LTD4. A subthreshold concentration of LTE4 reduced responses to LTC4 and LTD4. LY171883 and WY-48252 competitively antagonized LTD4-induced contractions of vena cava. In contrast, these antagonists blocked contractions to LTC4 in a biphasic manner. Lower segments of the LTC4 concentration-response curves were less affected than the upper portion suggesting the possibility of 2 LTC4 receptor subtypes. Our results indicate that LTE4 is a weak or partial agonist in this tissue and furthermore they suggest a lack of high affinity receptors for LTE4 favoring LTC4 and LTD4. Indomethacin did not influence contractions to the leukotrienes or histamine. However, the response to U46619 was greatly enhanced suggesting release of a vasodilator prostaglandin as part of the overall response of the vena cava to the thromboxane A2 mimetic.
Rinkema
L E
LE
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Roman
C R
CR
VanAlstyne
E L
EL
Spaethe
S M
SM
Fleisch
J H
JH
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D015777:Eicosanoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006912:Hydroxyquinolines / Q000494:pharmacology; D066298:In Vitro Techniques; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017999:Leukotriene E4 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors; D013777:Tetrazoles / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014682:Vena Cava, Inferior / Q000187:drug effects*
D000098:Acetophenones; D015777:Eicosanoids; D006912:Hydroxyquinolines; D011450:Prostaglandin Endoperoxides, Synthetic; D013189:SRS-A; D013777:Tetrazoles; C056398:Wy 48252; D017997:Leukotriene C4; D013928:Thromboxane A2; D011189:Potassium Chloride; D017999:Leukotriene E4; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D006632:Histamine; C044660:LY 171883