Leukotriene D4 increases both the force of contraction and polyphosphoinositide formation in guinea-pig papillary muscle.
Leukotriene D4 (LTD4) increased the force of contraction in guinea-pig papillary muscle. A rapid (less than 1 min), transient (less than 5 min) response to LTD4 (1 microM) reached 19.3 +/- 5.4% of isoproterenol maximum. A single exposure to LTD4 resulted in complete and homologous desensitization which was not influenced by indomethacin. LTD4 (0.1-3.0 microM) increased total inositol phosphates released from [3H]inositol-labeled tissue. ICI 198,615, a selective LT receptor antagonist, blocked both the increase in force of contraction and the increase in inositol phosphates by LTD4, but had no effect on the inotropic response to isoproterenol. These data support the existence of specific functional LTD4 receptors in myocardial tissue of guinea-pigs.
Falcone
R C
RC
Philadelphia College of Pharmacy and Science, Department of Pharmacology and Toxicology, PA 10104.
Moore
W C
WC
Aharony
D
D
Scott
A L
AL
Siegl
P K
PK
Orzechowski
R F
RF
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D007191:Indazoles; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D013189:SRS-A; C054217:ICI 198615; D007545:Isoproterenol; D007213:Indomethacin