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

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Abstract

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. 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 μM. Neither dimaprit (H2-receptor selective) nor R-α-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 μM. 3 pA2 experiments were performed to obtain KB values of chlorpheniramine (H1-receptor selective) and diphenhydramine (H1-receptor selective) for blocking histamine-stimulate relaxation of nasal mucosae. K B values for chlorpheniramine (0.87 nM) and diphenhydramine (7.4 nM) were consistent with their interaction at the Hi-receptor type. Additionally, neither 10 μM cimetidine (H2-receptor selective) nor 1 μM thioperamide (H3-receptor selective) had any effect on the relaxation curve for histamine. In the presence of 10 μM indomethacin (cyclo-oxygenase inhibitor), histamine caused a maximal relaxation response of 73 ± 5% of the noradrenaline-induced tone with an EC5O value of 2.9 ± 0.2 μM, which was not different from control values (EC 50 = 5.0 ± 0.4 μM; maximal relaxation = 71 ± 6%). In contrast, 200 μM NG-nitro-L-arginine (nitric oxide synthase inhibitor) completely inhibited histamine-induced relaxation of nasal mucosae. In conclusion, data from the present study suggest only the H 1-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.

Original languageEnglish
Pages (from-to)269-276
Number of pages8
JournalAutonomic and Autacoid Pharmacology
Volume22
Issue number5-6
DOIs
StatePublished - Oct 2002

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Histamine Receptors
Nasal Mucosa
Histamine
Nitric Oxide
Guinea Pigs
Histamine H1 Receptors
Norepinephrine
Histamine H3 Receptors
Chlorpheniramine
Diphenhydramine
Histamine H2 Receptors
thioperamide
Blood Vessels
Betahistine
Dimaprit
Methylhistamines
Cyclooxygenase Inhibitors
Nitroarginine
Histamine Antagonists
Cimetidine

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Pharmacology

Cite this

Histamine receptor type coupled to nitric oxide-induced relaxation of guinea-pig nasal mucosa. / Bockman, Charles; Zeng, W.

In: Autonomic and Autacoid Pharmacology, Vol. 22, No. 5-6, 10.2002, p. 269-276.

Research output: Contribution to journalArticle

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abstract = "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. 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 μM. Neither dimaprit (H2-receptor selective) nor R-α-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 μM. 3 pA2 experiments were performed to obtain KB values of chlorpheniramine (H1-receptor selective) and diphenhydramine (H1-receptor selective) for blocking histamine-stimulate relaxation of nasal mucosae. K B values for chlorpheniramine (0.87 nM) and diphenhydramine (7.4 nM) were consistent with their interaction at the Hi-receptor type. Additionally, neither 10 μM cimetidine (H2-receptor selective) nor 1 μM thioperamide (H3-receptor selective) had any effect on the relaxation curve for histamine. In the presence of 10 μM indomethacin (cyclo-oxygenase inhibitor), histamine caused a maximal relaxation response of 73 ± 5{\%} of the noradrenaline-induced tone with an EC5O value of 2.9 ± 0.2 μM, which was not different from control values (EC 50 = 5.0 ± 0.4 μM; maximal relaxation = 71 ± 6{\%}). In contrast, 200 μM NG-nitro-L-arginine (nitric oxide synthase inhibitor) completely inhibited histamine-induced relaxation of nasal mucosae. In conclusion, data from the present study suggest only the H 1-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.",
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