Differential rank order of potency for antagonism of LTC4- and LTD4-induced contractions of guinea pig trachea.
In the presence of 1-serine-borate complex (SB), employed to prevent LTC4 to LTD4 metabolism, desamino-2-nor-LTE, [4-hydroxy-5-[(2,2-carboxyethyl)thio]-6-nonadecenoic acid; DN-LTE1] equally antagonized the contractions elicited by LTC4 (-log KB = 5.8 +/- 0.2) and LTD4 (-log KB = 5.5 +/- 0.4) on the isolated guinea pig trachea. In contrast, FPL 55712 preferentially antagonized the LTD4-induced contractions in the presence of SB with a -log KB = 6.2 +/- 0.2, whereas only weak antagonism of the LTC4-induced contractions was observed (-log KB = 4.9 +/- 0.2). Thus, the rank order of potency for antagonizing the LTC4-induced contractions was DN-LTE1 greater than FPL 55712, whereas the rank order for antagonizing LTD4 was FPL 55712 greater than DN-LTE1. On tissues pretreated with 10 microM FPL 55712 without SB, 10 microM DN-LTE1 antagonized the contractions elicited by LTC4 but not those elicited by LTD4. Thus, based upon the differential rank order of antagonism of the LTC4- and LTD4-induced contractions by these LT antagonists under two different experimental conditions, these results imply the existence of multiple LT receptors in the guinea pig trachea.
D000818:Animals; D001881:Borates / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology; D013189:SRS-A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012694:Serine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D001881:Borates; D002867:Chromones; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin; D013189:SRS-A; C040900:serine-borate complex; D012694:Serine; C006312:FPL 55712; C049906:4-hydroxy-5-((2-carboxyethyl)thio)-6-nonadecenoic acid