Global ETD Search

1	Characterization of a novel histamine G protein-coupled receptor from Schistosoma mansoni (SmGPCR) Mousa, Aisha H. January 2002 (has links) A G protein-coupled receptor with structural characteristics of a biogenic amine GPCR was cloned from Schistosoma mansoni (SmGPCR). SmGPCR was codon-optimized and double-tagged with FLAG and His epitopes at the N- and C-terminal ends, respectively. Immunofluorescence experiments targeting these epitopes revealed that the expression of codon-optimized SmGPCR was highly increased compared to wild-type in mammalian cells. These studies also demonstrated that SmGPCR has a typical GPCR topology, the N-terminus being extracellular and C-terminus intracellular. Functional assays revealed that codon-optimized SmGPCR was responsive only to histamine, which caused a dose-dependent increase in intracellular Ca2+ (EC50 = 0.54 +/- 0.05 muM), but not cAMP, consistent with a Gq pathway of signal transduction. In vitro behavioral studies showed that treatment of S. mansoni cercaria with exogenous histamine caused a dose-dependent increase in the motility of the parasite. Histamine -- Receptors. Antihistamines.
2	Characterization of a novel histamine G protein-coupled receptor from Schistosoma mansoni (SmGPCR) Mousa, Aisha H. January 2002 (has links) No description available. Histamine -- Receptors. Antihistamines.
3	Impact of Postexercise Hyperemia on Glucose Regulation in Humans Pellinger, Thomas Kent, 1970- 09 1900 (has links) xvii, 168 p. : ill. A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / An acute bout of moderate-intensity dynamic exercise results in a sustained rise in skeletal muscle blood flow from that of pre-exercise levels. This postexercise skeletal muscle hyperemia is mediated by two histamine receptors (subtypes, H 1 and H 2 ). Skeletal muscle glucose uptake is also enhanced, in an insulin-independent manner, following moderate-intensity dynamic exercise. The impact of skeletal muscle hyperemia on glucose regulation following exercise has yet to be examined. Therefore, the purpose of this dissertation was to determine if postexercise skeletal muscle hyperemia plays a substantial role in glucose regulation in humans. In Chapter III I tested my ability to block local H 1 - and H 2 -receptors located in the vastus lateralis muscle in humans. The results demonstrate that I was able to successfully block the increase in local blood flow evoked by compound 48-80 with the combination of the H 1 -receptor antagonist pyrilamine and the H 2 -receptor antagonist cimetidine, administered via skeletal muscle microdialysis. In Chapter IV I sought to determine the effect of local combined H 1 - and H 2 -receptor blockade, administered via skeletal muscle microdialysis, on postexercise interstitial glucose concentrations. My findings indicate postexercise delivery of glucose to the interstitial space of the previously active skeletal muscle is mediated, in part, by local H 1 - and H 2 -receptors. In Chapter V I examined the effect of oral administration of H 1 - and H 2 -receptor antagonists on glucose regulation following a postexercise oral glucose load. The results showed that the glycemic and insulin responses to postexercise oral glucose load were more sustained with H 1 - and H 2 -receptor blockade versus control, suggesting a histaminergic effect on postexercise glucose regulation. / Adviser: John Halliwill Physiology Microdialysis Histamine receptors Blood flow Postexercise hyperemia Glucose
4	Identification of Histamine Receptors in the Canine Gastrointestinal Tract Sullivant, Alyssa Martin 09 December 2016 (has links) The role of histamine in chronic gastrointestinal diseases has been increasingly recognized in humans, but the role of histamine in the canine gastrointestinal tract has not been thoroughly investigated. The presence and distribution of all 4 histamine receptors (H1, H2, H3, and H4) in the stomach, duodenum, ileum, jejunum, and colon of healthy dogs were evaluated with a commonly employed immunohistochemistry technique using antibodies predicted to cross react with canine histamine receptors. All 4 histamine receptors were identified in the canine gastrointestinal tract, and differed in location and density within sections of the canine gastrointestinal tract. Antibody specificity was evaluated with Western blot. With the establishment of a method to study histamine receptors in the canine gastrointestinal tract, additional research to evaluate histamine receptors in dogs is warranted to further understand the pathophysiology and treatment of chronic canine enteropathies. canine inflammatory bowel disease H4 H3 H2 H1 histamine receptors
5	Investigation of solubility and dissolution of famotidine from solid glass dispersions of xylitol Mummaneni, Vanaja 01 January 1988 (has links) The solubility and dissolution of famotidine from solid glass dispersions of xylitol, prepared by the fusion method, were investigated. Preliminary stability studies revealed that famotidine was stable for 72 hours (< 0.5% decomposition) in water at 37° ± 0.5° C. Both the drug and the carrier were stable and did not decompose during the fusion process. About 4% decomposition of famotidine was observed after 72 hours in an aqueous solution of famotidine:xylitol glass dispersion at 37° ± 0.5° C. Solubility of famotidine from solid glass dispersions and physical mixtures with famotidine:xylitol ratios of 1:1, 1:20 and 1:40 was studied at 37° ± 0.5° C and found to be higher than that of famotidine alone in water. The solubility of famotidine from physical mixtures increased linearly with the increase in xylitol concentration, but the relationship was not linear for glass dispersions. The dispersions were more effective in enhancing the solubility of famotidine as compared to physical mixtures of corresponding drug:carrier ratios. A 1:40 glass dispersion increased the solubility by up to 32% while the solubility increase from a 1:40 physical mixture was 14%. Dissolution studies were carried out on glass dispersions with famotidine:xylitol ratios of 1:1, 1:10 and 1:20 in water at 37° ± 0.5° C. Results revealed a marked increase in the dissolution rate of famotidine from solid glass dispersions when compared to the dissolution rate of plain famotidine powder alone. The increase was greatest at the lowest drug level (1:20 drug:carrier ratio) with 100% of the drug dissolving within one minute. The glass dispersions were subjected to thermal analysis. Thermograms obtained by differential scanning calorimetry showed no evidence of chemical interaction between famotidine and xylitol. Phase diagrams were constructed for famotidine:xylitol solid glass dispersions and physical mixtures from melting temperatures determined by the capacity tube method. The phase diagram of the dispersion system suggested the formation of a eutectic mixture of famotidine and xylitol near a drug:carrier ratio of 1:40. Famotidine Solubility Xylitol Histamine Receptors Pharmaceutical chemistry Chemistry Medicinal and Pharmaceutical Chemistry Medicine and Health Sciences Pharmacy and Pharmaceutical Sciences Physical Sciences and Mathematics
6	Homology modeling and structural analysis of the antipsychotic drugs receptorome López Muñoz, Laura 22 June 2010 (has links) Classically it was assumed that the compounds with therapeutic effect exert their action interacting with a single receptor. Nowadays it is widely recognized that the pharmacological effect of most drugs is more complex and involves a set of receptors, some associated to their positive effects and some others to the side effects and toxicity. Antipsychotic drugs are an example of effective compounds characterized by a complex pharmacological profile binding to several receptors (mainly G protein-coupled-receptors, GPCR). In this work we will present a detailed study of known antipsychotic drugs and the receptors potentially involved in their binding profile, in order to understand the molecular mechanisms of the antipsychotic pharmacologic effects.The study started with obtaining homology models for all the receptors putatively involved in the antipsychotic drugs receptorome, suitable for building consistent drug-receptor complexes. These complexes were structurally analyzed and compared using multivariate statistical methods, which in turn allowed the identification of the relationship between the pharmacological properties of the antipsychotic drugs and the structural differences in the receptor targets. The results can be exploited for the design of safer and more effective antipsychotic drugs with an optimum binding profile. / Tradicionalmente se asumía que los fármacos terapéuticamente efectivos actuaban interaccionando con un único receptor. Actualmente está ampliamente reconocido que el efecto farmacológico de la mayoría de los fármacos es más complejo y abarca a un conjunto de receptores, algunos asociados a los efectos terapéuticos y otros a los secundarios y toxicidad. Los fármacos antipsicóticos son un ejemplo de compuestos eficaces que se caracterizan por unirse a varios receptores simultáneamente (principalmente a receptores unidos a proteína G, GPCR). El trabajo de la presente tesis se ha centrado en el estudio de los mecanismos moleculares que determinan el perfil de afinidad de unión por múltiples receptores de los fármacos antipsicóticos.En primer lugar se construyeron modelos de homología para todos los receptores potencialmente implicados en la actividad farmacológica de dichos fármacos, usando una metodología adecuada para construir complejos fármaco-receptor consistentes. La estructura de estos complejos fue analizada y se llevó a cabo una comparación mediante métodos estadísticos multivariantes, que permitió la identificación de asociaciones entre la actividad farmacológica de los fármacos antipsicóticos y diferencias estructurales de los receptores diana. Los resultados obtenidos tienen interés para ser explotados en el diseño de fármacos antipsicóticos con un perfil farmacológico óptimo, más seguros y eficaces. Receptor 5-HT2A Receptor D3 Receptor D2 Ligando Clozapina Derivados Benzofuranonas Risperidona Olanzapina esquizofrenia métodos de regresión campos de interacción Molecular (MIF) Perfil Multireceptorial modelado por homología Docking sitio de unión interacciones moleculares selectividad afinidad de unión Diana Meta-Diana efectos secundarios fármaco antipsicótico típico fármaco antipsicótico atípico agonista antagonista membrana receptoroma rhodopsina estructura de rayos X descriptores moleculares farmacología análisis multivariante procedimiento integrado Computer-aided drug design Integrated approach Multivariate analysis Pharmacology Molecular descriptors X-ray structure Rhodopsin Receptorome Membrane Antagonist Agonist Atypical antipsychotic drug Typical antipsychotic drug Side effects Off-target Target Selectivity Binding affinity Molecular interactions Binding site Homology modeling Docking Multireceptor profile Molecular interaction Field (MIF) Partial Least Squares (PLS) Principal Component Analysis (PCA) Schizophrenia Benzolactam Derivatives Benzofuranone Derivatives Risperidone Olanzapine Clozapine Ligand Adrenergic receptors Muscarinic receptors Histamine receptors Serotonin receptors Dopamine receptors beta2-Adrenergic receptor D2 receptor D3 receptor 5-HT2A receptor G protein-coupled receptors (GPCR) 57

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