Inhibition of ovalbumin-induced allergic rhinitis by sumatriptan through the nitric oxide pathway in mice

Life Sci. 2019 Nov 1:236:116901. doi: 10.1016/j.lfs.2019.116901. Epub 2019 Oct 11.

Abstract

Aims: Allergic rhinitis is a global cause of disability, characterized by airway inflammation. Sumatriptan is a 5-hydroxytryptamine 1B/1D (5HT1B/1D) agonist used as a treatment for migraine headaches. Activation of 5HT1B/1D receptors can inhibit the release of neuropeptides and inhibit the inflammation cascades. This study investigated the effect of sumatriptan on ovalbumin-induced allergic rhinitis model in mice and the role of nitric oxide.

Methods: Female Balb/c mice were sensitized by intraperitoneal ovalbumin and challenged by intranasal ovalbumin. Mice received sumatriptan in doses 3, 10, 30 μg/kg intraperitoneally, 30 min before the last ovalbumin challenge.

Key findings: Intraperitoneal injection of sumatriptan significantly decreased the nasal scratching, IL-4 and serum IgE levels of allergic mice, but it increased IFNγ levels. Histopathological analysis showed that the number of eosinophils was significantly elevated in nasal mucosa of ovalbumin-induced allergic mice, while sumatriptan treatment significantly reduced the number of eosinophils. GR-127935, a selective 5-HT1B/1D-receptor antagonist, reversed the anti-allergic effects of sumatriptan. Acute administration of l-NAME, a non-specific inhibitor of nitric oxide synthase, along with sumatriptan attenuated the anti-allergic effects of sumatriptan but chronic administration of l-NAME did not affect the influences of sumatriptan. Furthermore, sumatriptan decreased the inducible nitric oxide synthase (iNOS) protein expression in allergic mice, but it did not change the concentration of eNOS protein.

Significance: This study shows that sumatriptan administration is associated with anti-allergic effects which are through 5HT1B/1D receptors. Decrease in iNOS expression and changes in T-helper 1&2 cytokines levels may indicate the involvement of inducible NOS and inflammation.

Keywords: 5HT1B/1D receptors; Allergic rhinitis; Mice; Nitric oxide; Sumatriptan.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type II / metabolism*
  • Ovalbumin / toxicity*
  • Rhinitis, Allergic / chemically induced
  • Rhinitis, Allergic / metabolism
  • Rhinitis, Allergic / pathology
  • Rhinitis, Allergic / prevention & control*
  • Serotonin 5-HT1 Receptor Agonists / pharmacology*
  • Signal Transduction / drug effects*
  • Sumatriptan / pharmacology*

Substances

  • Serotonin 5-HT1 Receptor Agonists
  • Nitric Oxide
  • Sumatriptan
  • Ovalbumin
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse