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In vitro effects of H 1 ‐antihistamines on histamine and PGD 2 release from mast cells of human lung, tonsil, and skin
Author(s) -
Okayama Y.,
Benyon R. C.,
Lowman M. A.,
Church M. K.
Publication year - 1994
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.1994.tb02657.x
Subject(s) - histamine , terfenadine , ketotifen , mast cell , immunoglobulin e , prostaglandin d2 , pharmacology , azelastine , cetirizine , chemistry , tryptase , tonsil , immunology , endocrinology , medicine , prostaglandin , asthma , antibody
Mast cells from different anatomic sites differ in cytochemistry and response to various secretory stimuli. We have investigated whether responsiveness to the second‐generation H 1 ‐receptor antagonists, which are important first‐line drugs for the relief of symptoms in patients with chronic urticaria and allergic rhinoconjunctivitis, also differs according to the site of origin of mast cells. The effects of terfenadine, ketotifen, and cetirizine were therefore examined in relation to the IgE‐dependent release of histamine and prostaglandin D 2 (PGD 2 ) from dispersed human lung, tonsil, and skin mast cells. Terfenadine had a biphasic effect on lung and skin mast cells: at low concentrations, a concentration‐dependent inhibition of histamine release from lung and skin mast cells was observed, whereas at higher concentrations the drug stimulated mediator release. Even at a high concentration, terfenadine inhibited mediator release from tonsil mast cells. Ketotifen had low potency as an inhibitor of mediator release from lung and tonsil mast cells. In skin mast cells, no inhibition of mediator release was observed below 1.0 μM, and above that concentration it induced mediator release. Cetirizine, a much less lipophilic drug than the others tested, did not induce mediator release from mast cells even at concentrations up to 100 μM. This drug showed concentration‐dependent inhibition of IgE‐dependent mediator release from lung and tonsil mast cells only. Our results show that human mast cells are heterogeneous with respect to modulation of mediator release by these H 1 ‐antihistamines. In particular, differences were observed between skin mast cells and those dispersed from lung and tonsils.