Mast cell degranulation mediates bronchoconstriction via serotonin and not via renin release

Manne Krop, ZG Ozunal, W (Wenxia) Chai, Rory de Vries, Durk Fekkes, AM Bouhuizen, Ingrid Van den Berg - Garrelds, Jan Danser

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To verify the recently proposed concept that mast cell-derived renin facilitates angiotensin II-induced bronchoconstriction bronchial rings from male Sprague-Dawley rats were mounted in Mulvany myographs, and exposed to the mast cell degranulator compound 48/80 (300 mu g/ml), angiotensin I. angiotensin II, bradykinin or serotonin (5-hydroxytryptamine, 5-HT), in the absence or presence of the renin inhibitor aliskiren (10 mu mol/l), the ACE inhibitor captopril (10 mu mol/l), the angiotensin II type 1 (AT(1)) receptor blocker irbesartan (1 mu mol/l), the mast cell stabilizer cromolyn (0.3 mmol/l), the 5-HT2A/2C receptor antagonist ketanserin (0.1 mu mol/l) or the alpha(1)-adrenoceptor antagonist phentolamine (1 mu mol/l). Bath fluid was collected to verify angiotensin generation. Bronchial tissue was homogenized to determine renin, angiotensinogen and serotonin content. Compound 48/80 contracted bronchi to 24 +/- 4% of the KCI-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 the bath fluid after 48/80 exposure were below the detection limit. Angiotensin I and II equipotently contracted bronchi. Captopril shifted the angiotensin I curve approximate to 10-fold to the right, whereas irbesartan fully blocked the effect of angiotensin II. Bradykinin-induced constriction was shifted approximate to 100-fold to the left with captopril. Serotonin contracted bronchi, and ketanserin fully blocked this effect. Finally, bronchial tissue contained serotonin at micromolar levels, whereas renin and angiotensinogen were undetectable in this preparation. In conclusion, mast cell degranulation results in serotonin-induced bronchoconstriction, and is unlikely to involve renin-induced angiotensin generation. (C) 2010 Elsevier B.V. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)185-189
Number of pages5
JournalEuropean Journal of Pharmacology
Issue number1-3
Publication statusPublished - 2010

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