PMID- 7672000 OWN - NLM STAT- MEDLINE DCOM- 19951018 LR - 20190624 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 278 IP - 2 DP - 1995 May 15 TI - Effect of azelastine on airway hyperresponsiveness mediated by stimulated macrophages. PG - 161-6 AB - The effect of the anti-allergic drug azelastine, 4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepine-4-yl)-1-(2H)-phth alazione), on airway hyperresponsiveness induced by immunologically stimulated pulmonary alveolar macrophages was investigated in canine bronchial segments under isometric conditions in vitro. Macrophages stimulated with anti-dinitrophenyl immunoglobulin E (IgE) antibody and dinitrophenyl-human serum albumin potentiated the contractile responses to electrical field stimulation at all frequencies, an effect that was abolished by azelastine (3 x 10(-5) M). In contrast, azelastine had no effect on the potentiation of the contractile responses to electrical stimulation by U46619, a thromboxane A2 mimetic. The IgE-mediated release of thromboxane A2 from macrophages was inhibited by azelastine in a concentration-dependent fashion, the maximal decrease and the concentration required to produce a half-maximal effect being 84 +/- 6% (P < 0.001) and 16 microM, respectively. These results suggest that azelastine may attenuate macrophage-induced parasympathetic airway hyperresponsiveness through an inhibition of the release of thromboxane A2. FAU - Tamaoki, J AU - Tamaoki J AD - First Department of Medicine, Tokyo Women's Medical College, Japan. FAU - Takemura, H AU - Takemura H FAU - Tagaya, E AU - Tagaya E FAU - Sakai, A AU - Sakai A FAU - Yamawaki, I AU - Yamawaki I FAU - Konno, K AU - Konno K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Histamine H1 Antagonists) RN - 0 (Phthalazines) RN - 0 (Prostaglandin Endoperoxides, Synthetic) RN - 0 (Serum Albumin) RN - 0 (Vasoconstrictor Agents) RN - 37341-29-0 (Immunoglobulin E) RN - 57576-52-0 (Thromboxane A2) RN - 76898-47-0 (15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid) RN - ZQI909440X (azelastine) SB - IM MH - 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid MH - Animals MH - Bronchial Hyperreactivity/*physiopathology MH - Dogs MH - Electric Stimulation MH - Female MH - Histamine H1 Antagonists/*pharmacology MH - Immunoglobulin E/immunology MH - In Vitro Techniques MH - Isometric Contraction/drug effects MH - Macrophage Activation/drug effects MH - Macrophages, Alveolar/*physiology MH - Male MH - Parasympathetic Nervous System/drug effects MH - Phthalazines/*pharmacology MH - Prostaglandin Endoperoxides, Synthetic/pharmacology MH - Serum Albumin/immunology MH - Synaptic Transmission/drug effects MH - Thromboxane A2/analogs & derivatives/metabolism/pharmacology MH - Vasoconstrictor Agents/pharmacology EDAT- 1995/05/15 00:00 MHDA- 1995/05/15 00:01 CRDT- 1995/05/15 00:00 PHST- 1995/05/15 00:00 [pubmed] PHST- 1995/05/15 00:01 [medline] PHST- 1995/05/15 00:00 [entrez] AID - 0014-2999(95)00114-Z [pii] AID - 10.1016/0014-2999(95)00114-z [doi] PST - ppublish SO - Eur J Pharmacol. 1995 May 15;278(2):161-6. doi: 10.1016/0014-2999(95)00114-z.