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The mechanism of LTE 4 ‐induced histamine hyperresponsiveness in guinea‐pig tracheal and human bronchial smooth muscle, in vitro
Author(s) -
Jacques Crawford A.J.,
Spur Bernd W.,
Johnson Malcolm,
Lee Tak H.
Publication year - 1991
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.1476-5381.1991.tb12518.x
Subject(s) - histamine , leukotriene d4 , medicine , endocrinology , carbachol , guinea pig , acetylcholine , cholinergic , biology , bronchial hyperresponsiveness , histaminergic , leukotriene , chemistry , stimulation , lung , asthma , respiratory disease
1 Preincubation of guinea‐pig tracheal smooth muscle with leukotriene E 4 (LTE 4 ) in vitro increased its subsequent responsiveness to histamine. 2 LTE 4 pretreatment of guinea‐pig tracheal strips did not affect the subsequent responsiveness to either the contractile agents, carbachol and KCl, or to the relaxant β‐adrenoceptor agonist, isoprenaline. 3 LTE 4 ‐induced airway histamine hyperresponsiveness was blocked by indomethacin (5 μ m ), GR32191 (3 μ m ), atropine (1 μ m ) and tetrodotoxin (1 μ m ). 4 U46619, a stable thromboxane A 2 ‐analogue, at a non‐contractile concentration of 4 n m , increased tracheal smooth muscle sensitivity to histamine. 5 Both LTE 4 and U46619 pretreatment increased the contractile response of tracheal smooth muscle to electrical field stimulation. 6 Preincubation of human bronchial spirals with LTE 4 in vitro increased its subsequent responsiveness to histamine. 7 LTE 4 ‐induced histamine hyperresponsiveness of human bronchus was inhibited by GR32191 (3 μ m ) and atropine (1 μ m ). 8 It is proposed that LTE 4 induces guinea‐pig airway smooth muscle hyperresponsiveness to histamine via a facilitation of cholinergic neurotransmission, which is dependent upon the secondary generation of prostanoid mediator(s) acting on TP‐receptors situated on cholinergic nerve terminals. In addition, it is suggested that LTE 4 may induce histamine hyperresponsiveness of human bronchus in vitro by a similar mechanism as to that seen in guinea‐pig central airway smooth muscle.