Thesis (M.S.)--University of Wisconsin--Madison, 1983. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 21-23).

Proefschrift - Utrecht. / Summary in Dutch and English.

Thesis (M.S.)--University of Wisconsin--Madison, 1964. / eContent provider-neutral record in process. Description based on print version record. Bibliography: l. 35-36.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph.D.)--Boston University / Compounds known to be histaminane inhibitors in vitro were studied for their ability to potentiate certain pharmacological effects of histamine. If histaminase plays a limiting role in the biological responses to histamine, histaminase inhibitors could serve as pharmacological tools in attempts to elucidate the problem of the possible physiological role of this naturally occurring and biologically highly active amine. The available information on histamine metabolism, histaminase (diamine oxidase), and histaminase inhibitors, was reviewed. The latter may be grouped into: 1) carbonyl reagents (semi-carbazides, hydroxylamines, hydrazines), and 2) substituted or unsubstituted diamines and guanidines. Recent evidence (Schayer et al. 1952, 1953) shows that aminoguanidine and other histaminase inhibitors block the major catabolic pathway of histamine in rats and, to a certain extent, in guinea pigs. Iproniazid (a hydrazine), a potent inhibitor of amine oxidase, blocks the main catabolic pathway of histamine in mice and cats. These two metabolic pathways for histamine catabolism are distinct and apparently related to different enzyme systems. In very recent reports, histaminase inhibitors are said to act as specific potentiators of histamine in the response of highly sensitive smooth muscle preparations (Arunlakshana et al. 1954; Lindel & Westling, 1954; D.J. Smith, 1953). The reported degree of potentiation is small, but it is not clear whether this is due to the same original high sensitivity of the tissue, wich may act as a limiting factor. The published results do not establish that the reported effect is related to inhibition of histaminase, since the possibility is not excluded that the compounds may act as sensitizers of histamine receptors on smooth muscle for which they appear to have some affinity (Ariens, 1954). [TRUNCATED]

Thesis (M.S.)--University of Wisconsin--Madison, 1982. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Four aspects of the function of histaminergic systems were studied in the rat brain: toxicology, catabolism, release in vivo, and high affinity binding of histamine. Preparations of histamine-N-methyltransferase (HNMT) derived from kidney and brain were employed in the radioenzymatic quantification of histamine in biological samples. Tritiated S-adenosyl-L-methionine ([³H]-SAM) served as the co-substrate. A toxicological study was conducted to determine the sensitivity of the HA innervation to prenatal treatment with methylazoxymethanol (MAM), an inhibitor of mitosis. In adult rats, the MAM treatment was without effect on cerebral histamine content, although forebrain HNMT activity was 50% reduced. In another study, C-57 mice were treated with the selective dopamine neurotoxin l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Substantial dopamine depletions were not associated with alterations in the cerebral histamine content. In a study of the structural requirements for HNMT inhibition, 9-amino-1,2,3,4-tetrahydroacridine (THA), was found to be one of the most potent inhibitors yet described. The β-carboline alkaloids, of which harmaline is the prototype, were also found to be moderately potent HNMT inhibitors. Because of the lack of high-affinity re-uptake and the absence of alternate catabolic pathways, blockade of HNMT can potentially alter central histaminergic tone. Peripheral administration of THA was able to produce dose-dependent increases in cerebral histamine content, as was the more potent HNMT inhibitor, metoprine. The issue of structural requirements for HNMT inhibition are discussed in the light of these results. The in vivo release of histamine was studied by the cerebral microdialysis technique. After chronic implantation of horizontal probes, TTX-insensitive and partially calcium-sensitive efflux of histamine was detected in the dorsal striatum and the bed nucleus of the stria terminalis. In striatum, histamine efflux was elevated 50% after peripheral histidine loading (500 mg/kg, i.p.). After synthesis blockade with α-fluoromethylhistidine (100 mg/kg,i.p.), extracellular histamine levels in striatum disappeared in a bi-exponential manner. The half-lives of this disappearance, 32 minutes and 7 hours, indicate the presence of at least two histamine pools. Striatal histamine efflux was elevated by yohimbine treatment (10 mg/kg, i.p.), suggesting the presence of a tonic α₂-adrenergic inhibition of histamine release in vivo. In addition to the classical H₁ and H₂ receptors, histamine is able to bind to a pharmacologically distinct site, H₃, recently characterized as an autoreceptor regulating the synthesis and release of histamine. The binding properties of the H₃ ligand [³H]-N[symbol omitted]-methylhistamine ([³H]-N-MeHA) were studied in forebrain cryostat sections by autoradiography. Determination of Bmax (25 fmole/section) and displacement studies indicated that [³H]-N-MeHA bound to the same site as [³H]-histamine: the high affinity histamine binding site. Binding was greatest in the basal ganglia and had a complex distribution within the cerebral cortex. Quinolinic acid lesion studies indicated that the majority of the binding in the basal ganglia was on striato-nigral projection neurons. Cortical binding was also sensitive to local excitotoxic lesions. Therefore, the majority of H₃ binding is located on postsynaptic structures intrinsic to these brain regions, rather than on presynaptic autoreceptors on terminals of histamine neurons. / Medicine, Faculty of / Graduate

No description available.

Thesis (M.A.)--Boston University / Histamine liberation has long been associated with mast cells both in anaphylaxis and chemically induced histamine release. Although the work on intact animals and in vitro preparations did much to clarify conditions under which histamine is released, these preparations were not ideal. A proper experimental design would be one in which the mast cells were isolated from other tissue influences. With this in mind, the present investigations were carried out. Mast cells were isolated from the peritoneal fluid of the rat and aivided into aliquots. In this preparation of morphologically and physiologically intact mast cells, the effects of specific antigen and compound 48/80 were studied on isolated cells in an attempt to learn more about the mechanism of histamine release from the mast cell. [TRUNCATED]

Afhandling (M.D.)--Copenhagen. / Summary in English and Danish. Bibliography: p. [101]-114.