Histamine receptor type coupled to nitric oxide-induced relaxation of guinea-pig nasal mucosa.

Bockman CS; Zeng W

摘要

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.

机译：1这项研究的目的是表征从豚鼠的鼻粘膜血管床的介导的组胺受体类型，并确定环氧酶产物和一氧化氮在这种松弛剂对组胺的反应中的作用。这些研究是在体外检查的分离的鼻粘膜中进行的，以获得组胺受体型选择性激动剂的效力，从而导致血管瘤化并确定组胺受体拮抗剂的亲和力，以抑制组胺诱导的松弛。 2鼻粘膜与去甲肾上腺素的收缩后，组胺导致最大弛豫反应，为75 +/- 6％，占由去甲肾上腺素引起的收缩，平均EC50值为4.3 +/- 0.5微米。 DIMAPRIT（H2受体选择性）和R-α-甲基组织胺（H3受体选择性）均未引起鼻粘膜的显着松弛。相比之下，β-受体选择性（H1受体选择性）引起81 +/- 7％的去甲肾上腺素诱导的张力，EC50值为15 +/- 1 microM。进行了3个PA2实验，以获得氯 - 受体选择性）和二苯胺（H1受体选择性）的Kb值，以阻止组胺刺激的鼻粘膜松弛。氯苯胺（0.87 nm）和二苯胺（7.4 nm）的Kb值与H1受体类型的相互作用一致。此外，10 microm cimetidine（H2受体选择性）和1 microm硫代酰胺（H3受体选择性）对组胺的弛豫曲线没有任何影响。 4在存在10 microm吲哚美辛（环氧酶抑制剂）的情况下，组胺引起的最大弛豫反应为73 +/- 5％的去甲肾上腺素诱导的张力，EC50值为2.9 +/- 0.2 microM，这并不差异从控制值（EC50 = 5.0 +/- 0.4 microm;最大弛豫= 71 +/- 6％）。相比之下，200 microm ng-硝基-l-精氨酸（一氧化氮合酶抑制剂）完全抑制了组胺诱导的鼻粘膜松弛。 5总之，本研究的数据仅表明H1受体类型介导鼻粘膜血管的松弛到组胺，而组胺诱导的鼻粘膜弛豫完全取决于一氧化氮的产生。

Histamine receptor type coupled to nitric oxide-induced relaxation of guinea-pig nasal mucosa.

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