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71 Activation of mglur7 attenuates the development of allergy-induced anaphylaxis
  1. T Gao1
  1. 1Uppsala Universitet, Neuroscience, Uppsala, Sweden

Abstract

Background and aims Allergy is a common condition that is caused by an overreaction of the immune system to foreign substances. Severe allergic reactions can result in a systemic life-threatening state referred to as an anaphylactic shock. The progression of the anaphylactic reaction is hard to control after onset, and there is no effective prophylactic treatment available. Recently, mice deficient of the group III metabotropic glutamate receptor mGluR7 were shown to display an anaphylactic-like behaviour when exposed to peripheral histamine, suggesting that mGluR7 works as a neuronal brake on peripheral neurons involved in allergy and anaphylaxis. However, the role of mGluR7 in allergen-induced anaphylaxis is still unknown.

Methods In the PCA model, on the first day, BALB/C mice were lightly anaesthetised with isoflurane and their left ears were intradermally (i.d.) injected with a monoclonal antibody (IgE directed against OVA- trinitrophenol (TNP), 1 µg in 10 µl PBS), whereas the right ears were used as controls (receives an i.d. injection of 10 µl PBS as vehicle). The PCA reaction was induced 24 hours later by an intravenous injection of 50 µg OVA-TNP in 200 µl of 2% Evans blue in PBS.

Results Here, we show that central activation of mGluR7 dampens the development of allergen-induced anaphylaxis as intrathecal, but not intraperitoneal, prophylactic administration of the mGluR7 allosteric agonist N, N’-dibenzhydrylethane-1, 2-diamine dihydrochloride [ML1] AMN082 attenuated the development of passive cutaneous anaphylaxis in mice.

Conclusions Activating the mGluR7 system thus represents a potential preventive treatment for anaphylaxis.

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