Pulmonary, Gastrointestinal and Urogenital Pharmacology Mast cell degranulation mediates bronchoconstriction via serotonin and not via renin release

abstract Article history:Received 13 January 2010Received in revised form 7 April 2010Accepted 24 April 2010Available online 10 May 2010Keywords:Mast cellBronchoconstrictionReninAngiotensinSerotonin To verify the recently proposed concept that mast cell-derived renin facilitates angiotensin II-inducedbronchoconstriction bronchial rings from male Sprague–Dawley rats were mounted in Mulvany myographs,and exposed to the mast cell degranulator compound 48/80 (300 µg/ml), angiotensin I, angiotensin II,bradykinin or serotonin (5-hydroxytryptamine, 5-HT), in the absence or presence of the renin inhibitoraliskiren (10 µmol/l), the ACE inhibitor captopril (10 µmol/l), the angiotensin II type 1 (AT 1 ) receptor blockerirbesartan (1 µmol/l), the mast cell stabilizer cromolyn (0.3 mmol/l), the 5-HT 2A/2C receptor antagonistketanserin (0.1 µmol/l) or the α 1 -adrenoceptor antagonist phentolamine (1 µmol/l). Bath fluid was collectedto verify angiotensin generation. Bronchial tissue was homogenized to determine renin, angiotensinogen andserotonin content. Compound 48/80 contracted bronchi to 24±4% of the KCl-induced contraction.Ketanserin fully abolished this effect, while cromolyn reduced the contraction to 16±5%. Aliskiren,captopril, irbesartan and phentolamine did not affect this response, and the angiotensin I and II levels in thebath fluid after 48/80 exposure were below the detection limit. Angiotensin I and II equipotently contractedbronchi. Captopril shifted the angiotensin I curve ≈10-fold to the right, whereas irbesartan fully blocked theeffect of angiotensin II. Bradykinin-induced constriction was shifted ≈100-fold to the left with captopril.Serotonin contracted bronchi, and ketanserin fully blocked this effect. Finally, bronchial tissue containedserotonin at micromolar levels, whereas renin and angiotensinogen were undetectable in this preparation. Inconclusion, mast cell degranulation results in serotonin-induced bronchoconstriction, and is unlikely toinvolve renin-induced angiotensin generation.© 2010 Elsevier B.V. All rights reserved.