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β‐Adrenoceptors mediate inhibition of [ 3 H]‐acetylcholine release from the isolated rat and guinea‐pig trachea: role of the airway mucosa and prostaglandins
Author(s) -
Wessler Ignaz,
Reinheimer Torsten,
Brunn Gernot,
Anderson Gary P.,
Maclagan Jennifer,
Racké Kurt
Publication year - 1994
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.1476-5381.1994.tb17128.x
Subject(s) - acetylcholine , isoprenaline , propranolol , endocrinology , guinea pig , medicine , chemistry , muscarinic acetylcholine receptor , antagonist , stimulation , hexamethonium , biology , receptor
1 Rat or guinea pig isolated tracheae were labelled with [ 3 H]‐choline to measure evoked tritium outflow, which reflects neuronal release of [ 3 H]‐acetylcholine. Tritium outflow was evoked either by electrical stimulation of the extrinsic vagal nerve (rat tracheae) or by 27 m m potassium (guinea pig tracheae). 2 In rat tracheae isoprenaline (0.01, 0.1 μ m ) inhibited evoked [ 3 H]‐acetylcholine release, whereas β‐adrenoceptor‐selective agonists (fenoterol, formoterol, salbutamol) were ineffective. 3 The inhibitory effect of isoprenaline was abolished under the following conditions: (i) presence of propranolol (1 μ m ) or of the β‐selective antagonist CGP 20712 A (0.1 μ m ); (ii) removal of the mucosa at the start of the experiments; (iii) blockade of cyclooxygenase activity by 3 μ m indomethacin. 4 In rat isolated tracheae prelabelled with [ 3 H]‐arachidonic acid, isoprenaline (0.1 μ m ) but not formoterol (0.01 μ m ) enhanced the outflow of [ 3 H]‐prostaglandins (PGD 2 , PGE 2 ). This effect was blocked by 0.1 μ m CGP 20712 A. 5 In guinea pig tracheae electrical stimulation of the extrinsic vagal nerve did not cause a constant release of [ 3 H]‐acetylcholine, but 27 m m potassium elicited a reproducible release of [ 3 H]‐acetylcholine. In this species both isoprenaline (0.1 μ m ) and formoterol (0.01 μ m ) inhibited evoked [ 3 H]‐acetylcholine release. Inhibition was abolished under the following conditions: (i) presence of propranolol (1 μ m ) or of the β 2 ‐selective antagonist ICI 118551 (0.3 μ m ); (ii) removal of the mucosa at the start of the experiments; (iii) blockade of cyclooxygenase activity by 3 μ m indomethacin. 6 In conclusion, the present experiments have demonstrated that activation of β‐adrenoceptors localized in the mucosa mediates inhibition of [ 3 H]‐acetylcholine release from the neuroeffector junctions of the pulmonary, parasympathetic nerves most probably by the liberation of inhibitory prostaglandins from the airway mucosa. The adrenoceptor subtype involved differs in rat (β 1 subtype) and guinea pig (β 2 subtype) airways.