Premium
Contractile activity of three endothelins (ET‐1, ET‐2 and ET‐3) on the human isolated bronchus
Author(s) -
Advenier C.,
Sarria B.,
Naline E.,
Puybasset L.,
Lagente V.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12071.x
Subject(s) - nicardipine , endothelins , endothelin 1 , contraction (grammar) , endothelin 3 , endocrinology , acetylcholine , chemistry , medicine , bronchus , endothelin receptor , calcium , biology , receptor , respiratory disease , lung
1 The effects of three endothelins: (i) the classical or human/porcine endothelin (ET‐1); (ii) [Trp 6 , Leu 7 ] endothelin (ET‐2) and (iii) [Thr 2 , Phe 4 , Thr 5 , Tyr 6 , Lys 7 , Tyr 14 ] endothelin or rat endothelin (ET‐3) were tested on the human isolated bronchus. 2 ET‐1 produced a concentration‐dependent contraction of the human isolated bronchus that proceeded in two different steps. The first step was observed at very low concentrations (pD 2 = 11.01 ± 0.17, n = 10) but corresponded to a low intrinsic activity (E max = 15.6 ± 1.8% of E max induced by acetylcholine (ACh) 3 × 10 −3 m , n = 10). This effect was potentiated by Bay K 8644 10 −7 m (E max = 26.1 ± 2.9% of ACh 3 × 10 −3 m , n = 5, P < 0.05), reduced by nicardipine 10 −6 m (E max = 6.0 ± 2.6% of ACh 3 × 10 −3 m , n = 5, P < 0.05) and strongly inhibited in calcium‐free medium. The second step of the action of ET‐1 corresponded to a lesser potency (pD 2 = 7.90 ± 0.17, n = 9) but a higher intrinsic activity (E max = 82.5 ± 4.7% of ACh 3 × 10 −3 m ). This effect was not significantly modified by nicardipine 10 −6 m or by Bay K 8644 10 −7 m . Neither of the two effects was modified by indomethacin 3 × 10 −6 m . 3 The effects of ET‐2 and ET‐3 were qualitatively similar to those of ET‐1 but quantitatively different; for these two steps of contracting activity and for potency and efficacy the ranking was: ET‐1 > ET‐2 = ET‐3. 4 Thus, ET‐1 appears to be the most potent of these three substances in its effect on the human isolated bronchus. Its activity seems to involve the action of voltage‐dependent calcium channels at low concentrations (10 −12 to 10 −9 m ), whereas other mechanisms are involved at higher concentrations (10 −8 to 3 × 10 −7 m ).