组胺H3受体诱导豚鼠灌注细支气管的支气管扩张：上皮的作用

Bronchodilatation of guinea-pig perfused bronchioles induced by the H3-receptor for histamine: role of epithelium.

Burgaud J L, Oudart N

Laboratoire de Pharmacologie, UFR de Pharmacie, Limoges, France.

Br J Pharmacol. 1993 Aug;109(4):960-6. doi: 10.1111/j.1476-5381.1993.tb13714.x.

Abstract

The influence of epithelium on the effects of H3-histamine receptor agonist (R)alpha-methylhistamine [(R)alpha-MeHist] on airways was investigated on the guinea-pig perfused bronchioles. 2. In preparations under resting tone, removal of the bronchiolar epithelium or treatment with the cyclo-oxygenase inhibitor indomethacin (10(-5) M) increased the constriction induced by histamine and acetylcholine in a concentration-dependent manner without an alteration of the K(+)-induced contraction. 3. In this preparation (R)alpha-MeHist induced a concentration-dependent bronchodilatation which was antagonized in a competitive manner by thioperamide (an H3-antagonist) with a pA2 value of 8.6. 4. This bronchodilatation was reversed to a low concentration-dependent constriction after either removal of the epithelium or treatment with indomethacin (10(-5) M) but was unaffected by both 10(-5) M tranylcypromine (an inhibitor of PGI2 synthesis) and 5 x 10(-5) M NG-nitro-L-arginine methyl ester (an inhibitor of NO synthesis). 5. It is suggested that, in guinea-pig perfused bronchioles (R)alpha-MeHist induces an epithelium-dependent relaxation via the release of metabolite(s) of arachidonic acid.

摘要

在豚鼠灌注细支气管上研究了上皮对H3组胺受体激动剂（R）α-甲基组胺[（R）α-MeHist]气道效应的影响。2. 在静息张力下的制备中，去除细支气管上皮或用环氧化酶抑制剂吲哚美辛（10^-5 M）处理，可使组胺和乙酰胆碱诱导的收缩以浓度依赖性方式增加，而K+诱导的收缩无改变。3. 在此制备中，（R）α-MeHist诱导浓度依赖性支气管舒张，硫代哌啶（一种H3拮抗剂）以竞争性方式拮抗该舒张，pA2值为8.6。4. 去除上皮或用吲哚美辛（10^-5 M）处理后，这种支气管舒张转变为低浓度依赖性收缩，但不受10^-5 M反苯环丙胺（一种PGI2合成抑制剂）和5×10^-5 M NG-硝基-L-精氨酸甲酯（一种NO合成抑制剂）的影响。5. 提示在豚鼠灌注细支气管中，（R）α-MeHist通过释放花生四烯酸代谢产物诱导上皮依赖性舒张。