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. 1993 Feb;108(2):448–452. doi: 10.1111/j.1476-5381.1993.tb12824.x

A novel ETA-receptor antagonist, FR 139317, inhibits endothelin-induced contractions of guinea-pig pulmonary arteries, but not trachea.

L O Cardell 1, R Uddman 1, L Edvinsson 1
PMCID: PMC1907966  PMID: 8448595

Abstract

1. The effects of a proposed endothelin-receptor antagonist, FR 139317, on the contraction induced by endothelin-1, endothelin-2 and endothelin-3, were analysed on isolated circular segments of pulmonary arteries and rings of trachea from the guinea-pig. 2. The pharmacological profiles of endothelin-1 and endothelin-2 were almost identical in the guinea-pig pulmonary artery, whereas endothelin-3 demonstrated a weaker and less potent contractile effect. The contractions induced by endothelin-1 and endotheliln-2 were competitively antagonized by FR 139317. Schild plot analysis revealed a straight line with a slope that did not differ from unity. The pA2 value was 6.65. In contrast, the endothelin-3 induced contractile response was unaffected by FR 139317. 3. In tracheal segments endothelin-1, endothelin-2 and endothelin-3 evoked contractions of similar magnitude and sensitivity. FR 139317 had no effect on the endothelin-induced contractions in tracheal segments. 4. In ring segments of pulmonary artery and trachea, potassium, noradrenaline and histamine caused concentration-dependent contractile effects. These contractions were not modified by FR 139317 in the concentration range 10(-7) to 3 x 10(-6)M. 5. FR 139317 seems to be a selective ETA-receptor antagonist which competitively antagonizes the endothelin-1- and endothelin-2-induced contractions of guinea-pig isolated pulmonary arteries. Thus, the guinea-pig pulmonary artery appears to be endowed with one receptor type (ETA) which is antagonized by FR 139317 and with another endothelin-receptor subtype which responds to endothelin-3, but is not antagonized by FR 139317.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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