Shimadzu ASMS 2017 Wednesday Breakfast Seminar 

"Imaging the distribution of selective GABAA receptor modulators in the asthmatic lung using MALDI imaging mass spectrometry"

Subtype-selective GABA_A receptor (GABA_AR) modulators have been shown to relax pre-contracted human airway smooth muscle and alleviate airway hyperresponsiveness in a murine model of asthma.^{1, 2}  Further lead development resulted in modulators with limited CNS distribution and additional anti-inflammatory effects.  The pharmacological effects of these compounds are mediated by different lung cell types (including white blood cells that have been shown to express discrete GABA_AR subtypes).  Pharmacokinetic analysis demonstrated excellent long lasting concentrations of GABA_AR modulators in the lung. Herein, we present the spatial lung distribution of GABA_AR modulators using imaging mass spectrometry (IMS).³ This new MALDI IMS technique provides spatial and molecular specificity by detecting a unique m/z for the analyte of interest at specific coordinates within the tissue section. In concert with immunohistochemistry, marking the expression of different GABA_AR subunits, IMS-microscopy fusion enables visualization of drug-receptor interactions ex vivo. Other IMS-microcopy fusion images will be presented based on H&E and periodic acid fluorescent Schiff’s tissue stains to visualize distribution and localization of GABA_AR modulators in the lung. 

Margaret L. Guthrie, Ph.D. candidate 

University of Wisconsin - Milwaukee