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Bitter taste is one of the five basic taste modalities, and is mediated by 25 bitter taste receptors (T2Rs) in humans. How these few receptors recognize a wide range of structurally diverse bitter compounds is not known. To address this question, structural and functional studies on T2Rs are necessary. Quinine is a natural alkaloid and one of the most intense bitter tasting compounds. Previously it was shown that quinine activates T2R4, however, whether T2R4 has only one binding site for quinine, and the amino acids on the receptor involved in binding to quinine remain to be determined. In this study, the ligand binding pocket on T2R4 for quinine was characterized using a combination of approaches. These included molecular model guided site-directed mutagenesis, characterization of the expression of the mutants by flow cytometry, and functional characterization by cell based calcium imaging. Twelve mutations were made in T2R4 and their expression and function were characterized. Results show that the ligand binding pocket of T2R4 for quinine is situated on the extracellular side, and is formed by the residues present on the transmembrane regions TM3, TM4, and extracellular loop regions ECL2 and TM6-ECL3-TM7 interface. Further, this study identified the following amino acids : A90, F91, Y155 N173, T174, Y258 and K270 to play an important role in quinine binding to T2R4. The detailed study of residues interacting with ligand will help in understanding how various ligands interact with T2Rs, and facilitate the pharmacological characterization of potent antagonists or bitter taste blockers. The characterization of novel ligands, including bitter taste blockers will help in dissecting the signaling mechanism(s) of T2Rs, and help in the development of novel therapeutic tools for the food and drug industry.

This dissertation examines the literary responses to the British “good taste” movement in the work of Aldous Huxley, Evelyn Waugh, and John Betjeman. Bolstered by the increased prominence and influence of design experts in the early-twentieth century, critics and designers sought to improve public taste in Britain. The didactic and rhetorical strategies these taste reformers employed gradually convinced Britons that their nation, which lagged behind its European neighbours in accepting modern design, was in the throes of a “taste crisis.” The increased authority of design experts, the public enthusiasm for decoration, and the growth of the market for household goods led not only to a widespread fascination with design, but also to the formulation of an increasingly narrow and orthodox definition of “good taste.” I analyze these authors’ critical and literary writing, relying, in many cases, on their unpublished or neglected work in order to reveal the development of their taste theories. I argue that these writers, dissatisfied with what they perceived to be the “good taste” movement’s stultifying and homogenizing effects, produced a “dissident” taste theory in reaction to the consensual and codified notion of “good taste.” Chapter One considers Huxley’s often overlooked role as the editor of House & Garden magazine in the context of his early fiction and his gradual conversion to mysticism. Chapter Two examines the architectural novels of Evelyn Waugh, noting, in particular, the inherent tensions he navigated between modernity and tradition, Philistinism and theory, theology and aesthetics. Chapter Three studies John Betjeman’s roles as critic, poet, guide-book writer, and preservationist, charting the development of his tastes from international modernism to local eclecticism. Rather than accepting the easy distinctions between “good and bad” taste, Huxley, Waugh, and Betjeman—themselves so often criticized for being unyieldingly absolute in their worldviews—attempted instead to articulate a “taste between,” one that fused the aesthetic, ethical, and psychic components of taste in an imaginative spectrum, rather than an orthodox system.

This dissertation examines the literary responses to the British “good taste” movement in the work of Aldous Huxley, Evelyn Waugh, and John Betjeman. Bolstered by the increased prominence and influence of design experts in the early-twentieth century, critics and designers sought to improve public taste in Britain. The didactic and rhetorical strategies these taste reformers employed gradually convinced Britons that their nation, which lagged behind its European neighbours in accepting modern design, was in the throes of a “taste crisis.” The increased authority of design experts, the public enthusiasm for decoration, and the growth of the market for household goods led not only to a widespread fascination with design, but also to the formulation of an increasingly narrow and orthodox definition of “good taste.” I analyze these authors’ critical and literary writing, relying, in many cases, on their unpublished or neglected work in order to reveal the development of their taste theories. I argue that these writers, dissatisfied with what they perceived to be the “good taste” movement’s stultifying and homogenizing effects, produced a “dissident” taste theory in reaction to the consensual and codified notion of “good taste.” Chapter One considers Huxley’s often overlooked role as the editor of House & Garden magazine in the context of his early fiction and his gradual conversion to mysticism. Chapter Two examines the architectural novels of Evelyn Waugh, noting, in particular, the inherent tensions he navigated between modernity and tradition, Philistinism and theory, theology and aesthetics. Chapter Three studies John Betjeman’s roles as critic, poet, guide-book writer, and preservationist, charting the development of his tastes from international modernism to local eclecticism. Rather than accepting the easy distinctions between “good and bad” taste, Huxley, Waugh, and Betjeman—themselves so often criticized for being unyieldingly absolute in their worldviews—attempted instead to articulate a “taste between,” one that fused the aesthetic, ethical, and psychic components of taste in an imaginative spectrum, rather than an orthodox system.

Pain sensitivity is typically reduced in individuals with higher blood pressure although the nature of this relationship is poorly understood. Relatedly, the ingestion of sweet tasting solutions has been shown to reduce pain, possibly by an opioid mediated mechanism. The objective of the present research was to investigate the effects of blood pressure and sweet taste on pain sensitivity in healthy adults. The first aim was to test whether blood pressure interacts with sweet taste to affect pain sensitivity. The second aim was to test whether endogenous opioids mediate the effects of sweet taste and blood pressure on pain. In Study One, participants held sweet, bitter and plain water solutions in their mouths during exposure to a painful cold pressor test. Replicating previous research, individuals with higher blood pressure were found to have generally higher pain tolerance than those with lower blood pressure. Sweet taste was associated with an increase in pain tolerance but only in individuals with lower range blood pressure, increasing their tolerance to the level of those with higher blood pressure. In Study Two, participants held sweet solution, plain water or nothing in their mouths during cold pressors on two days. To test the involvement of endogenous opioids, participants were administered an opioid antagonist on one of the test days. Participants with higher resting blood pressure again showed increased tolerance and reduced unpleasantness ratings of the pain tasks, as well as dampened mood reactivity to the testing. In these individuals, the opioid antagonist reduced their pain tolerance and partially reversed their lower mood reactivity. As in Study One, sweet taste increased pain tolerance in participants with lower but not higher blood pressure, but this was unaffected by opioid blockade. Taken together these results suggest some overlap between non-opioid mechanisms of sweet taste and blood pressure related analgesia. These results are also consistent with work suggesting that endogenous opioid activity may play a role in the reduced pain sensitivity, and perhaps mood reactivity, of individuals with higher blood pressure and that multiple processes are involved in blood pressure-related hypoalgesia.

Taste is detected by cells of taste buds in the oral cavity. Mammalian taste buds contain three types of cells: receptor, presynaptic, and glial-like. Of these three, glial-like cells are the least studied. Their only known function is that they clear neurotransmitters from the extracellular space. The present work describes two previously undocumented properties of glial-like cells. First, Oxytocin receptor (OXTR) mRNA was detected by RT-PCR in taste tissue of mice. In the taste buds of Oxtr-YFP knockin mice, YFP was seen in glial-like taste cells and other cells immediately outside the taste bud, but no other cells in oral epithelium. Oxytocin (OXT) elicited Ca2+ responses from cells that resemble glial-like taste cells (by criteria including gene expression and lack of excitability). The EC50 for OXT in these cells was 33 nM, and responses saturated at 1 µM. 500 nM L-371,257 (an OXTR antagonist) significantly inhihited the responses to OXT. In a semi-intact preparation of lingual slices, OXT did not alter bitter tastant-evoked Ca2+ responses. Further, in behavioral studies, OXT (10 mg/kg i.p.) did not alter the responses of mice to aversive salty (NaCl), bitter (quinine), or sour (citric acid) solutions. In contrast, OXT (0.1 mg/kg i.p.) significantly decreased taste behavioral responses to low-to-intermediate concentrations of sucrose. My data suggest that OXT may modulate sweet taste sensitivity in vivo by acting on glial-like cells in taste buds. Second, Renal Outer Medullary K channel (ROMK) mRNA was also detected by RT-PCR in taste buds . Immunostaining revealed that ROMK is localized to the apical tips of glial-like taste cells. In the kidney, ROMK, apically localized in nephron epithelium facilitates a unidirectional flow (i.e. excretion) of K+. I suggest that, analogous to glia in the central nervous system, glial-like taste cells homeostatically redistribute extracellular [K+ ] within taste buds to maintain their sensitivity. The results of this study reveal that glial-like taste cells resemble nervous system glia in more ways than simply clearing neurotransmitters. They may also modulate the sensory output of the taste bud and buffer the extracellular [K+]. A more active role for glial-like cells in the functioning of the taste bud should be investigated.

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [101]-111).

Thesis (PhD) -- AUT University, 2009. / Includes bibliographical references. Also held in print (xxiv, 222 leaves : charts ; 30 cm.) in the Archive at the City Campus (T 006.32 SOL)

Thesis (M.S.)--Rutgers University, 2009. / "Graduate Program in Food Science." Includes bibliographical references (p. 99-112).

Thesis (M.S.)--University of Michigan, 1979.