与一氧化氮诱导的豚鼠鼻黏膜舒张相关的组胺受体类型。
Histamine receptor type coupled to nitric oxide-induced relaxation of guinea-pig nasal mucosa.
作者信息
Bockman C S, Zeng W
机构信息
Department of Pharmacology, Creighton University School of Medicine, 2500 California Plaza, Criss III, Room 553, Omaha, NE 68178, USA.
出版信息
Auton Autacoid Pharmacol. 2002 Oct-Dec;22(5-6):269-76. doi: 10.1046/j.1474-8673.2002.00268.x.
1 The aim of this study was to characterize the histamine receptor type mediating relaxation of the vascular bed of the nasal mucosa from the guinea-pig, and to determine the role of cyclo-oxygenase products and nitric oxide in this relaxant response to histamine. These studies were performed in isolated nasal mucosae examined in vitro to obtain potencies of histamine receptor-type selective agonists in causing vasorelaxation and to determine affinities of histamine receptor antagonists for inhibiting histamine-induced relaxation. 2 After contraction of nasal mucosae with noradrenaline, histamine caused a maximal relaxation response that was 75 +/- 6% of the contraction caused by noradrenaline with a mean EC50 value of 4.3 +/- 0.5 microM. Neither dimaprit (H2-receptor selective) nor R-alpha-methylhistamine (H3-receptor selective) caused significant relaxation of nasal mucosae. In contrast, betahistine (H1-receptor selective) caused an 81 +/- 7% relaxation of noradrenaline-induced tone with an EC50 value of 15 +/- 1 microM. 3 pA2 experiments were performed to obtain KB values of chlorpheniramine (H1-receptor selective) and diphenhydramine (H1-receptor selective) for blocking histamine-stimulated relaxation of nasal mucosae. KB values for chlorpheniramine (0.87 nM) and diphenhydramine (7.4 nM) were consistent with their interaction at the H1-receptor type. Additionally, neither 10 microM cimetidine (H2-receptor selective) nor 1 microM thioperamide (H3-receptor selective) had any effect on the relaxation curve for histamine. 4 In the presence of 10 microM indomethacin (cyclo-oxygenase inhibitor), histamine caused a maximal relaxation response of 73 +/- 5% of the noradrenaline-induced tone with an EC50 value of 2.9 +/- 0.2 microM, which was not different from control values (EC50 = 5.0 +/- 0.4 microM; maximal relaxation = 71 +/- 6%). In contrast, 200 microM NG-nitro-L-arginine (nitric oxide synthase inhibitor) completely inhibited histamine-induced relaxation of nasal mucosae. 5 In conclusion, data from the present study suggest only the H1-receptor type mediates relaxation of nasal mucosal blood vessels to histamine, and histamine-induced relaxation of nasal mucosae is entirely dependent on nitric oxide production.
1 本研究的目的是鉴定介导豚鼠鼻黏膜血管床舒张的组胺受体类型，并确定环氧化酶产物和一氧化氮在组胺诱导的舒张反应中的作用。这些研究在体外分离的鼻黏膜上进行，以获得组胺受体类型选择性激动剂引起血管舒张的效能，并确定组胺受体拮抗剂抑制组胺诱导舒张的亲和力。2 用去甲肾上腺素使鼻黏膜收缩后，组胺引起最大舒张反应，该反应为去甲肾上腺素引起收缩的75±6%，平均EC50值为4.3±0.5微摩尔。地马普利（H2受体选择性激动剂）和R-α-甲基组胺（H3受体选择性激动剂）均未引起鼻黏膜明显舒张。相比之下，倍他司汀（H1受体选择性激动剂）使去甲肾上腺素诱导的张力舒张81±7%，EC50值为15±1微摩尔。3 进行pA2实验以获得氯苯那敏（H1受体选择性拮抗剂）和苯海拉明（H1受体选择性拮抗剂）阻断组胺刺激鼻黏膜舒张的KB值。氯苯那敏（0.87纳摩尔）和苯海拉明（7.4纳摩尔）的KB值与其在H1受体类型上的相互作用一致。此外，10微摩尔西咪替丁（H2受体选择性拮抗剂）和1微摩尔硫代哌啶（H3受体选择性拮抗剂）对组胺的舒张曲线均无影响。4 在10微摩尔吲哚美辛（环氧化酶抑制剂）存在下，组胺引起最大舒张反应为去甲肾上腺素诱导张力的73±%，EC50值为2.9±0.2微摩尔，与对照值（EC50 = 5.0±0.4微摩尔；最大舒张 = 71±6%）无差异。相比之下，200微摩尔NG-硝基-L-精氨酸（一氧化氮合酶抑制剂）完全抑制组胺诱导的鼻黏膜舒张。5 总之，本研究数据表明，仅H1受体类型介导鼻黏膜血管对组胺的舒张作用，且组胺诱导的鼻黏膜舒张完全依赖于一氧化氮的产生。
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