Browsing by Subject "Zinc"
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Item Applications of bis(imino)acenaphthene and investigation of boron arsenide as a high thermal conductivity material(2015-05) Evans, Daniel Anthony; Cowley, Alan H.; Jones, Richard A; Humphrey, Simon M; Anslyn, Eric V; Ekerdt, John GAbstract: Functionalization of the ubiquitous bis(imino)acenaphthene ligand class has been explored. The successful functionalization of this ligand type was found to be dependent upon the steric congestion encompassing the N-C-C-N fragment of the aryl substituted BIAN ligand. The sterically directed functionalization was found to proceed via either a radical backbone dearomatization route or a nucleophilic imine C-alkylation pathway. The structures of each of the functionalized BIAN derivatives were examined by means of single crystal X-ray crystallography. The foregoing reactions were also probed by EPR spectroscopy and DFT-D calculations in order to help elucidate the nature of the driving forces that are involved in BIAN functionalization. A series of aryl substituted BIAN zinc(II) chloride complexes were also prepared and their photophysical properties were investigated. Initially, four different methylated aryl substituents were examined, namely the 4-methylphenyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, and 2-methylphenyl derivatives. Examination of these four complexes revealed them to be non-emissive in solution. However, it was also determined that the 4-methylphenyl and 3,5-dimethylphenyl substituted complexes were emissive in the solid state. On the other hand, the 2,4,6-trimethylphenyl, and 2-methylphenyl complexes were found to be non-emissive in the solid state. The origins of the emissions of the foregoing complexes were also probed by means of TD-DFT calculations. The tuning of the stereoelectronic properties of a series of para-substituted aryl BIAN zinc(II) chloride complexes was undertaken with the view to modifying their solid state photophysical properties. For example, changing the electronic properties of the flanking para-substituted aryl substituents permitted tunability within the range of the red-orange-yellow emissions. Tunability was also achieved by employing a variety of different recrystallization techniques for growing the various structures, polymorphs, and solvatomorphs of each BIAN zinc(II) chloride complex. Boron arsenide, a somewhat neglected semiconductor compound, has been examined for its potential use as a high thermal conductivity material. High quality single crystal BAs microstructures have been synthesized and characterized by means of powder X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy, and scanning electron microscopy. The thermal conductivity properties of the BAs microstructures have been probed using microheater devices.Item Attenuation of elastic surface waves in thin films of superconducting zinc(Texas Tech University, 1978-05) Bailey, Wayne ElbertNot availableItem Characterization of the interactions of zinc with known and novel allosteric modulators of glycine receptor function(2016-12) Cornelison, Garrett Lee; Mihic, S. John; Aldrich, Richard W; Harris, R. Adron; Stavchansky, Salomon AThe glycine receptor is a member of the Cys-loop receptor superfamily of ligand-gated ion channels and is implicated as a possible therapeutic target for the treatment of diseases such as alcoholism and inflammatory pain. In humans, four glycine receptor subtypes (α1, α2, α3, and β) co-assemble to form pentameric channel proteins as either α homomers or αβ heteromers. To date, few agents have been identified that can selectively modulate the glycine receptor, especially those possessing subtype specificity. We used a cell-based method of phage display panning, coupled with two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes, to identify novel heptapeptide modulators of the α1β glycine receptor. Peptides were identified that act with selectivity on α1β and α3β compared to α2β glycine receptors. In addition, peptide activity at the glycine receptor decreased when zinc was chelated by tricine, similar to previous observations of a decrease in ethanol’s enhancing actions at the receptor in the absence of zinc. Zinc is an allosteric modulator of glycine receptor function, enhancing the effects of glycine at nanomolar to low micromolar concentrations, and inhibiting its effects at higher concentrations. As zinc is present physiologically at various concentrations within this range, it is capable of influencing glycine receptor function, including modulation by other pharmacological agents; however, the magnitude of this effect and its possible relevance are not known. I therefore investigated the utility of previously-described “zinc-enhancement insensitive” α1 glycine receptor mutants D80A, D80G, and W170S to probe for interactions between zinc and other allosteric modulators at the glycine receptor. Interestingly, I found that only the W170S mutation conferred complete abolishment of zinc enhancement across a variety of agonist and zinc concentrations. Using α1 W170S receptors, I established that in addition to ethanol, zinc also interacts with inhaled drugs of abuse, but not volatile anesthetics, to synergistically enhance channel function. Additionally, I determined that this interaction is abolished at higher zinc concentrations, when receptor-enhancing bindings sites are saturated, suggesting a mechanism by which modulators such as ethanol and inhalants are capable of increasing receptor affinity for zinc in addition to enhancing channel function on their own.Item A critical role for zinc in ethanol action at the glycine receptor(2012-05) McCracken, Lindsay Marie; Harris, R. Adron; Gore, Andrea; Duvauchelle, Christine; Morrisett, Richard; Trudell, JamesEthanol is a widely used drug, yet an understanding of its sites and mechanisms of action remains incomplete. Among the protein targets of ethanol are glycine receptors (GlyRs). In addition to ethanol, zinc also modulates GlyR function. Although the individual effects of zinc and alcohols on GlyR function have been well studied, the combined effects of these agents have not been thoroughly examined. This project investigated the effects of zinc on alcohol action at the glycine receptor (GlyR). In Aim 1, the effects of zinc on ethanol modulation of GlyR function were tested and characterized in three GlyR [alpha] subunits ([alpha]1-3). Aim 2 explored a site of action for the augmenting effects of zinc on ethanol action at the GlyR. Mutant D80A GlyRs, which lack a zinc binding site (D80), were constructed and allowed us determine if this zinc binding site is important for the zinc/ethanol interactions that were observed in Aim 1. The effects of ethanol were reduced in mutant D80A GlyRs compared to wild type (WT). In addition, manipulating zinc levels in our buffers either by adding or chelating zinc did not change the magnitude of ethanol enhancement of mutant D80A GlyRs as it did in WT GlyRs suggesting that the D80 position is important for zinc modulation of ethanol action. Finally, Aim 3 extended the findings from Aims 1 and 2 by evaluating the effects of a GlyR point-mutation on alcohol consumption and other behavioral tests in mice. Glra1(D80A) knock-in mice provided an animal model for behavioral studies of zinc/ethanol interactions at the GlyR and showed decreased alcohol consumption and preference compared to their WT littermates. In addition, D80A KI mice had increased startle responses compared to their WT littermates. Other behavioral tests were also conducted including tests of ethanol motor incoordination and strychnine induced convulsions; there were no differences detected between KI and WT mice in these assays. Overall, our findings demonstrate that zinc is critical in determining the effects of ethanol at GlyRs and suggest that zinc signaling at the D80 position may be important for mediating the behavioral effects of ethanol action at GlyRs.Item Effect of phytate added to a casein-based diet on endogenous zinc and study of pancreatic/biliary fluid fractions in rats(Texas Tech University, 1995-05) Kwun, In-SookThe purpose of the current research was to study the effect of phytate and Ca level on the endogenously secreted zinc. Sprague-Dawley rats (48) were fed a casein-based diet with added Na phytate containing either high (1.6 %) or low (0.8 %) Ca for 4 weeks to reduce the body Zn pool. After the depletion period, 65Zn was given IP to label the endogenous pool. Feces were collected for 3 wks (2 wks of the initial collection and 1 wk after dietary crossover). The ratios of excreted radioactivity phytate/non-phytate were determined as a measure of the phytate effect on endogenous zinc. Mean fecal 65Zn radioactivity was higher in the phytate, low Ca group (4582 ± 345 cpm/d) than in nonphytate, low Ca group (3990 ±215 cpm/d) during the initial collection period as well as during the crossover collection period, phytate group (3077 ±146 cpm/d) vs. non-phytate group (2376 ± 96 cpm/d) (p<0.0001). For the high Ca diets, the fecal 65Zn was higher for the phytate than the non-phytate during the 14 day collection (p<0.0001) but was not different after dietary crossover (p>0.05). Ratios of phytate/non-phytate ranged from 0.66-1.77 for low Ca diet and 0.64-1.99 for the high Ca diet. Since ratios above 1 represent a phytate effect on complexing endogenous Zn, this study showed phytate effect at both dietary Ca levels. At the elevated dietary Ca level, the phytate effect was synergized by dietary Ca (p<0.05). At the termination of the collection period, the common bile duct was cannulated with small bore tubing and pancreatic/biliary fluid collected with protein stimulation. Pancreatic/bniary fluid was applied to a Sephadex G-75 column and eluted with 0.01 mol/L Tris buffer, pH 8.1. Subfractions (2.5 mL) were collected for analysis of protein, total Zn concentration and 65Zn radioactivity. Distribution of protein in subfractions showed a peak corresponding to the high molecular weight protein standard (>66 kDa) in the pancreatic/biliary fluid. A more remarkable small molecular weight fraction was eluted near the 6.5 kDa protein standard. This demonstrates the presence of small molecular weight compounds in pancreatic/biliary fluid associated with zinc which may serve as ligands for the secretion of endogenous Zn into the duodenum. These ligands may dissociate Zn in the duodenum thus making it vulnerable to phytate complexation. It was estimated that the zinc concentration in the pancreatic/biliary fluid for one day (311.40 |ig/ day) was about 2.9 times greater than the zinc amount of dietary zinc consumed for one day (107.89 p-g/ day). Also, the dietary phytate group showed 72% of the zinc reabsorption which was enough to replace 63% of zinc which was secreted from pancreas for the zinc homeostasis.Item A protocol to evaluate the adsorptive removal of dissolved copper and zinc from highway runoff(2014-05) Ernst, Clayton Owen; Katz, Lynn EllenThe increasing urbanization of landscapes significantly alters the surface water hydrology of impacted watersheds. As a side effect, stormwater discharges to receiving water bodies are often of decreased quality due to pollutants deposited on impervious urban surfaces being entrained by runoff. A pertinent example of this problem is the presence of copper and zinc in highway runoff. Both copper and zinc have been shown to exert toxic effects on aquatic micro- and macro-biota. Copper in particular has been shown to harmfully disrupt the olfactory nervous system of fish species at concentrations as low as 3 [mu]g/L. To meet these limits, treatment of highway runoff for the removal of copper and zinc is necessary. However, due to the complexities associated with the behavior of heavy metals in natural systems, the appropriateness of removal techniques will necessarily depend on a variety of system-specific factors and chemical characteristics of highway runoff. Adsorption has been shown to be generally effective in the removal of dissolved heavy metals, but the choice of adsorptive media is again dependent on system-specific parameters. This study developed and evaluated a column testing protocol that can be used to quickly and reliably evaluate adsorptive removal of dissolved heavy metals from highway runoff. The protocol is demonstrated in an evaluation of iron oxide, manganese oxide, crab shell, concrete, and bone meal media for removing dissolved copper and zinc from highway runoff. The performance of these media was assessed as a function of various runoff characteristics including pH, ionic strength, alkalinity, and total organic carbon. The methodology was used to show that iron oxide media in combination with crab shell or concrete media provided the most effective removal of copper and zinc from highway runoff. Through this study, the convenience, flexibility, and robustness of the proposed protocol are compellingly established.Item Regulation of Zinc Transport in the Choroid Plexus(2014-07-21) Aquino, MayraThe choroid plexus epithelium forms the blood-cerebrospinal fluid barrier, but also accumulates and transports nutritive minerals, such as zinc, into and out of the cerebrospinal fluid. The goal of this thesis was to analyze interdependent regulation of zinc transporters with metallothionein as the choroid plexus epithelium adapts to increases or decreases in extracellular zinc. My first objective was to characterize time-dependent changes in zinc transporter and MT-1 expression as extracellular zinc was pharmacologically depleted or supplemented. My second objective was to characterize changes in zinc transporter and MT-1 expression in response to exposure to prolactin. My experimental approach was to analyze gene expression of ZnT1, Zip1, Zip6, MT-1 and carbonic anhydrase (CA-2) in primary cell cultures of neonatal rat choroid plexus and isolated tissues in which extracellular zinc was depleted with 10 ?M diethylene triamine pentaacetic acid or supplemented with 25 ?M ZnCl_(2) for 48 h. Gene expression was analyzed by fluorescence quantitative real-time polymerase chain reaction. Zinc accumulation studies indicate choroid plexus cells maintain capacity to accumulate zinc, even when zinc is chelated. In cells, zinc depletion decreased expression of MT-1 and ZnT1 at 3 h and increased Zip1 expression; Zip6 expression fluctuated. In isolated tissues, zinc depletion down-regulated MT-1 and ZnT1 expression, while up-regulating Zip1 and Zip6 expression. In cells, zinc supplementation induced MT-1, ZnT1 and Zip6 expression at 3 h. Zip1 expression decreased at 3 h. In isolated tissues zinc supplementation up-regulated MT-1 and ZnT1 expression, but did not alter Zip1 and Zip6 expression. These data indicate there is coordinated regulation of MT-1 and zinc transporters as extracellular zinc altered. Prolactin up-regulated gene expression of CA-2, MT-1, ZnT-1 and Zip6 in choroid plexus cells. The JAK/STAT inhibitor AG-490 increased CA-2 and MT-1 expression, but decreased ZnT1 and Zip6 expression. AG-490 further increased expression of CA-2 and MT-1 in prolactin treated cells. This suggests the JAK/STAT signaling pathway might tonically suppress basal expression of MT-1 and CA-2. AG-490 partially reversed up-regulation of ZnT-1 and Zip6 expression by prolactin. These data indicate there is a coordinated regulation of MT-1 and zinc transporters during extracellular zinc depletion or supplementation.Item The relationship between glycine receptor agonist efficacy and allosteric modulation(2014-05) Kirson, Dean; Mihic, S. JohnThe glycine receptor (GlyR) is a ligand-gated ion channel member of the cys-loop receptor superfamily, responsible for inhibitory neurotransmission in the brain and spinal cord. Both glycine and the partial agonist taurine act as endogenous ligands of the GlyR. Taurine-activated GlyR may have a role in the rewarding effects of drugs of abuse, such as ethanol. As a partial agonist, taurine has a decreased efficacy relative to glycine, resulting in a decreased maximum response. We investigated the effects of ethanol, anesthetics, inhalants, and zinc to determine if these allosteric modulators could increase the efficacy of the taurine-activated GlyR. Whole cell recordings of wild type GlyR revealed that each of the allosteric modulators potentiated currents generated by saturating concentrations of taurine but not glycine, implying an increase in efficacy. Zinc is found at GlyR-potentiating concentrations throughout the nervous system, so we examined the combinatorial effects of these allosteric modulators with zinc to mimic in vivo conditions. Whole cell recordings revealed that zinc potentiation of saturating taurine-generated currents decreased further potentiation by another allosteric modulator, indicating no synergistic effects on efficacy. We next investigated the actions of ethanol and isoflurane on the taurine-activated GlyR at the single channel level, finding that both allosteric modulators stabilized the channel open state, increasing the efficacy of the taurine-activated GlyR. We previously identified a mutation in the ligand-binding domain of the GlyR (D97R) that produces spontaneously activating channels, on which taurine has increased efficacy. We identified a residue, R131, as a possible binding partner of D97 in forming an electrostatic interaction that holds the channel in the closed state. We found that disruption of this interaction results in greatly increased taurine efficacy, indicating that efficacy for partial agonists may be determined by agonist ability to break this bond early in the activation process following binding. Thus we find differential mechanisms of allosteric modulation and efficacy determinations for the GlyR when activated by taurine vs. glycine.Item The relationship between glycine receptor agonist efficacy and allosteric modulation(2014-05) Kirson, Dean; Mihic, S. JohnThe glycine receptor (GlyR) is a ligand-gated ion channel member of the cys-loop receptor superfamily, responsible for inhibitory neurotransmission in the brain and spinal cord. Both glycine and the partial agonist taurine act as endogenous ligands of the GlyR. Taurine-activated GlyR may have a role in the rewarding effects of drugs of abuse, such as ethanol. As a partial agonist, taurine has a decreased efficacy relative to glycine, resulting in a decreased maximum response. We investigated the effects of ethanol, anesthetics, inhalants, and zinc to determine if these allosteric modulators could increase the efficacy of the taurine-activated GlyR. Whole cell recordings of wild type GlyR revealed that each of the allosteric modulators potentiated currents generated by saturating concentrations of taurine but not glycine, implying an increase in efficacy. Zinc is found at GlyR-potentiating concentrations throughout the nervous system, so we examined the combinatorial effects of these allosteric modulators with zinc to mimic in vivo conditions. Whole cell recordings revealed that zinc potentiation of saturating taurine-generated currents decreased further potentiation by another allosteric modulator, indicating no synergistic effects on efficacy. We next investigated the actions of ethanol and isoflurane on the taurine-activated GlyR at the single channel level, finding that both allosteric modulators stabilized the channel open state, increasing the efficacy of the taurine-activated GlyR. We previously identified a mutation in the ligand-binding domain of the GlyR (D97R) that produces spontaneously activating channels, on which taurine has increased efficacy. We identified a residue, R131, as a possible binding partner of D97 in forming an electrostatic interaction that holds the channel in the closed state. We found that disruption of this interaction results in greatly increased taurine efficacy, indicating that efficacy for partial agonists may be determined by agonist ability to break this bond early in the activation process following binding. Thus we find differential mechanisms of allosteric modulation and efficacy determinations for the GlyR when activated by taurine vs. glycine.Item Structural analysis and discovery of lead compounds for the fungal methionine synthase enzyme(2013-12) Ubhi, Devinder Kaur; Robertus, Jon D.Methionine synthases catalyze methyl transfer from 5-methyl-tetrahydrofolate (5-methyl-THF) to L-homocysteine (Hcy) in order to generate methionine (Met). Mammals, including humans, use a cobalamin dependent form, while fungi use a cobalamin independent protein called Met6p. The large structural differences between them make Met6p a potential anti-fungal drug target. Met6p is a 90 kDa protein with the active site located between two (βα)₈ barrels. The active site has a catalytic Zn²+ and binding sites for the two substrates, Hcy and folate. I present the crystal structures of three engineered variants of the Met6p enzyme from Candida albicans. I also solved Met6p in complex with several substrate and product analogs, including Hcy, Met, Gln, 5-methyl-THF-Glu₃ and Methotrexate-Glu₃ (MTX-Glu₃), and the bi-dentate ligand S-adenosyl homocysteine. Also described is a new fluorescence-based activity assay monitoring Hcy. Lastly, a high-throughput Differential Scanning Fluorimetry (DSF) assay was used to screen thousands of compounds in order to identify ligands which bind Met6p. My work details the mode of interaction of Hcy and folate with the Met6p protein. Several residues important to activity were discovered, like Asn 126 and Tyr 660, and proven to be important by site directed mutagenesis. Structural analysis revealed an important aspect of the mechanism. When Hcy binds to its pocket it makes strong ion pairs with the enzyme. In particular, 614 moves toward the substrate amine and triggers a rearrangement of active site loops; this draws the catalytic Zn²+ toward the Hcy thiol where a new ligand bond is formed, activating the thiol for methyl transfer. The work presented here lays the groundwork for structure based drug design and makes the development of Met6p specific bi-dentate ligands feasible. The fluorescence based activity assay I developed was successfully used to test the folate analog MTX-Glu₃, which inhibits with an IC₅₀ of ~4 mM. I also discovered our first bi-dentate ligand in the form of S-adenosyl homocysteine.Item Structural transformation rates in zinc-doped nickel fluorotitanate(Texas Tech University, 1983-12) Casey, Kelly GambleNot availableItem The effect of zinc on the β - adrenergic receptor in bovine satellite cells and the use of β - agonists and steroidal implants on muscle protein and mRNA levels in feedlot cattle(2013-05) Harris, Tyler; Johnson, Bradley J.; Ballou, Michael A.; Jackson, Samuel P.There are multiple methods cattle growers utilize in order to increase the amount of lean tissue deposition in feedlot cattle. β – adrenergic agonists are a commonly provided growth promotant that aids in increasing average daily gain (ADG), increasing animal efficiency, and increasing muscle mass. Ractopamine hydrochloride (RH) is a currently marketed β – agonist that is available for both steer and beef heifer use. Experiments were conducted implementing RH in an in vitro and in vivo environment. The in vitro study focused on the interactive effects of RH and the micromineral, zinc, on bovine satellite cells (BSC). While the in vivo study observed how RH and steroid hormones affect feedlot heifers. The in vitro experiment was designed to identify if zinc alters the binding affinity of RH to the β – agonist receptor. In order to determine if this interaction occurred, the concentration of cAMP produced by BSC was recorded in cells treated in a 2x2 factorial of either 0 or 1 μM zinc and 0 or 10 μM RH. Treatments were provided for short (6 h), mid (24), and long (96 h) time periods. Muscle related protein and mRNA levels were also measured in the study at 24 and 48 h. At 6 h, no differences (P >0.05) were detected in cAMP production between any of the treatments. However, at 24 h the 10 μM RH, 1 μM zinc treatment had a greater concentration of cAMP (P <0.05) compared to all other treatments. At 96 h the 10 μM RH, 0 μM zinc treatment had a lower concentration of cAMP (P =0.05) compared to the control. A tendency for an interaction of Zn and RH (P <0.10) was determined at 96 h. There were no significant results recorded from gene quantification methods. Genes of interest included the β1 adrenergic receptor, the β2 adrenergic receptor, AMPKα, myosin heavy chain I, myosin heavy chain IIA, and myosin heavy chain IIX. Protein quantification was performed via western blotting procedures two assess the abundance of the β1 adrenergic receptor and the β2 adrenergic receptor; however, no differences were detected in protein abundance between treatments. The in vivo experiment’s design was to determine the effects of a β-agonist and terminal implant date on feedlot heifer performance. It was our goal to determine the effect of implant strategy and β-agonist administration in beef feedlot heifers (n = 264). Terminal implants (TI; estradiol/trenbolone acetate implant, Component TE-200) were provided to heifers on day 0 of the trial (TI d 0), day 40 (TI d 40), and day 80 (TI d 80). The trial lasted for 140 days and animals that received the later two implants were first implanted on day 0 with Component TE-IH. The second treatment the cattle received was ractopamine-hydrochlorie (RH) in the form of Optaflexx® (OPT) over the final 28 days of the trial. Heifers either received no OPT (0 mg/head/d; No) or 200 mg/head/d (Yes) of OPT. Thirty animals were subjected to longissimus muscle (LM) biopsies on d 0, 40, 80, 112, and at slaughter on d 140 to view mRNA levels of myogenic related genes and protein quantities of the β1-adrenergic receptor (β1 AR) and β2-adrenergic receptor (β2 AR). On the same days, blood samples were taken from 108 animals to assess changes in plasma blood urea nitrogen (BUN), non-esterified fatty acids (NEFA) and progesterone due to treatments. Relative mRNA levels of myosin heavy chain IIX (MHC IIX), AMPKα, and IGF-I were increased (P < 0.05) in animals receiving a TI d 40 over the other two implant dates after RH was fed to animals. After RH administration myosin heavy chain IIA (MHC IIA) mRNA levels tended to decrease (P = 0.09) due to RH. An interaction between TI d and RH administration caused an increase (P < 0.05) in MHC IIA mRNA level in the TI d 80/Yes treatment group over all other treatments except the TI d 40/No treatment group. Protein intensity of the β2 AR was decreased (P < 0.05) by the latest TI d (TI d 80) during RH feeding, while β1 AR protein intensity tended to be lower (P < 0.10) in animals fed RH. BUN plasma levels were reduced (P < 0.05) after terminal implants and RH feeding; while progesterone was decreased (P < 0.05) by RH alone. Plasma NEFA levels were not affected by any treatment.Item Transverse-ultrasonic-attenuation determination of the energy gap between the normal and superconducting states of zinc.(Texas Tech University, 1975-05) Breashears, Eddie HearlNot availableItem Ultrasonic-attenuation determination of the anisotropic energy gap in superconducting zinc(Texas Tech University, 1973-05) Cleavelin, Cloves RinnNOT AVAILABLEItem Zinc interactions with allosteric modulators at the glycine receptor(2014-08) Cornelison, Garrett Lee; Mihic, S. JohnThe glycine receptor (GlyR) is a ligand-gated ion channel member of the Cys-loop receptor superfamily, responsible for inhibitory neurotransmission in the brain and spinal cord. Zinc is a potent allosteric modulator of GlyR function, enhancing GlyR activity at low nM to 10[mu]M concentrations while inhibiting GlyR activity at higher concentrations. We investigated sources of contaminating zinc, identifying low nM levels of zinc in ultrapure H₂O, powdered reagents used in the preparation of common electrophysiological buffers, and in polystyrene pipets. These low levels of zinc were capable of enhancing GlyR function. These findings suggest that without checking for this effect using a zinc-chelator such as tricine, one cannot assume that responses elicited by glycine applied alone are not necessarily also partially due to some level of allosteric modulation by zinc. Taurine-activated GlyR may have a role in the rewarding effects of drugs of abuse. Zinc is found at GlyR-potentiating concentrations throughout the nervous system, so we examined the combinatorial effects of zinc with drugs of abuse on taurine-activated GlyR to mimic in vivo conditions. Whole cell recordings revealed that zinc potentiation of saturating taurine-generated currents decreased further potentiation by drugs of abuse, indicating no synergistic effects on efficacy when receptors are saturated with taurine as may be seen during synaptic events in vivo. Finally, we utilized phage display to identify novel peptide modulators of the GlyR. We tested 26 peptides against [alpha1beta] GlyRs, identifying peptides with various levels of activity on GlyR function. We demonstrated that these modulators were zinc-dependent, as their effects on GlyR activity were abolished in the presence of the zinc-chelating agent tricine. Together, these data indicate the importance of accounting for the effects of zinc when studying the function of the GlyR, as even low levels of zinc that can be found as contaminants in labware and buffers can affect GlyR function and responses to various allosteric modulators, including drugs of abuse.