Browsing Theses and Dissertations by Author "Emamifar, Nick"
Effects Of T2r Activation On Different Lung Sensory SignalingEmamifar, NickPharmaceuticals are commonly bitter tasting and therefore may activate bitter taste receptors (T2Rs), which are canonically expressed in the taste buds of the tongue. An accumulation of recent evidence has suggested T2Rs carrying out a diverse set of non-tasting functions that are critical to the maintenance of homeostasis in extraoral locations throughout the body which give rise to the possibility of new medications to target these receptors. Using whole-cell patch-clamp recordings, the present study aims to illustrate how the bitter tasting pharmaceuticals, through the activation of T2Rs, modulate the neuroplasticity and therefore the function of lung sensory neurons. Three different airway irritants were used to activate pulmonary sensory receptors: zinc, an agonist for TRPA1; low pH or acid, an activator for both acid-sensing ion channels (ASICs) and TRPV1; and ATP, an agonist for P2X purinoceptors. Our results show that pretreatment with T2Rs activator chloroquine (0.01, 0.1 and 1 mM, 90 s) concentration-dependently potentiates zinc (30 µM, 3−16 s)-evoked TRPA1 currents and markedly inhibits ATP (0.3 or 1 µM, 4−6 s)-evoked P2X currents, whereas affects acid (pH 5.5 and pH 6.5, 4−16 s)-evoked inward currents differently: an inhibition for the slow inactivation ASIC-like current and a potentiation for the TRPV1-like current as well as the fast-inactivation ASIC current. Our results demonstrate that T2R activation in lung afferents has distinct modulatory effects on various ion channels that are sensitive to different airway irritants.