Characterization of the GABAA Receptor Subunits in a Murine Model of Asthma
Mentor 1
Dr. Alexander (Leggy) Arnold
Location
Union Wisconsin Room
Start Date
29-4-2016 1:30 PM
End Date
29-4-2016 3:30 PM
Description
The GABAA receptor is a heteropentameric ligand-gated ion channel consisting of combinations of 19 different subunits (α1–6, β1–3, γ1–3, δ, ε, π, θ, ρ). γ?aminobutyric acid (GABA) is the ligand that binds to the GABAA receptor and causes an inhibitory effect on the signal transduction cascade. Although predominantly located in the brain, recent studies have identified the receptor in immune cells, the epithelium and airway smooth muscles. Activated GABAA receptor present in the airway causes muscle relaxation and anti-inflammatory effects, hence can be a useful target for the management of asthma. Novel subtype selective GABAA receptor positive allosteric modulators with the potential to reduce inflammation and relax constricted airway smooth muscles in-vitro have been identified. To ascertain if the ovalbumin sensitized and challenged murine model of asthma is ideal for in-vivo testing of these compounds, we have characterized the expression of the different GABAA receptor subunits in asthmatic and non-asthmatic mice. We found expression in the smooth muscles, epithelium, and chondrocytes of the α4, α5, and β3 subunits. Expression for the α1 subunit was only expressed in the chondrocytes and the γ2 subunit showed no expression in the lungs.
Characterization of the GABAA Receptor Subunits in a Murine Model of Asthma
Union Wisconsin Room
The GABAA receptor is a heteropentameric ligand-gated ion channel consisting of combinations of 19 different subunits (α1–6, β1–3, γ1–3, δ, ε, π, θ, ρ). γ?aminobutyric acid (GABA) is the ligand that binds to the GABAA receptor and causes an inhibitory effect on the signal transduction cascade. Although predominantly located in the brain, recent studies have identified the receptor in immune cells, the epithelium and airway smooth muscles. Activated GABAA receptor present in the airway causes muscle relaxation and anti-inflammatory effects, hence can be a useful target for the management of asthma. Novel subtype selective GABAA receptor positive allosteric modulators with the potential to reduce inflammation and relax constricted airway smooth muscles in-vitro have been identified. To ascertain if the ovalbumin sensitized and challenged murine model of asthma is ideal for in-vivo testing of these compounds, we have characterized the expression of the different GABAA receptor subunits in asthmatic and non-asthmatic mice. We found expression in the smooth muscles, epithelium, and chondrocytes of the α4, α5, and β3 subunits. Expression for the α1 subunit was only expressed in the chondrocytes and the γ2 subunit showed no expression in the lungs.
