The role of supraspinal, spinal and peripheral alpha-2 adrenoceptors in the regulation of gastrointestinal motility in mice was investigated using anatomically site specific administration of clonidine and adrenoceptor antagonists. Clonidine produced a dose-dependent inhibition of gastrointestinal transit when given by the i.c.v., i.th., or s.c. routes, and was most potent when given i.c.v. Yohimbine, an alpha-2 adrenoceptor antagonist, but not the alpha-1 antagonist prazosin, antagonized the antitransit effects of clonidine. Yohimbine was most potent in antagonizing i.c.v. clonidine; increased doses of the i.c.v. antagonist were required when the agonist was given s.c. After transection of the spinal cord, i.th. clonidine failed to produce an antitransit effect. Additionally, the i.c.v. potency of clonidine decreased approximately 7-fold in spinally-transected mice. The data suggest that the antitransit effects of clonidine occur through actions at alpha-2 adrenoceptors located at both supraspinal and peripheral sites.

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Phospholipase C mediated hydrolysis of the phosphoinositides yields second messenger products which have been linked to normal and abnormal cell growth processes. It has been suggested that fatty acids may regulate phospholipase C activity in vivo. This study sought to investigate relationships between phospholipase C activity, tumor size and dietary linoleic and stearic acids.Phospholipase C activity, of livers and serially transplanted mammary adenocarcinomas from female strain A/ST mice on one of three diets, was measured. Tumors ranged from .20 to 2.98 g at the time of removal. Phospholipase C activity of tumors was negatively and significantly (p<.Ol) correlated to increasing tumor weight in those diet groups that contained linoleic acid and no added stearic acid. The highest PLC activity was seen in small tumors across all diet groups. Maximum PLC activity of tumors was over 2 fold higher than the maximum activity of livers across all diet groups. PLC activity of the liver was negatively and significantly (p<.02) correlated to increasing tumor weight for samples from the high linoleic acid diet (SF-15). This research concludes that PLC activity varies during tumorigenesis and may reflect tumor development. / Department of Biology

We hypothesize that brain glycogen, a stored form of glucose, may provide fuel for the brain conferring both negative and positive effects throughout the brain. The over accumulation of brain glycogen, or supercompensation, is hypothesized to exacerbate hypoglycemia associated autonomic failure (HAAF), promote memory and learning, and reduce neuron cell death during severe episodes of hypoglycemia. It was determined that brain glycogen supercompensation does occur in the mouse 6 hours following single and recurrent hypoglycemic episodes, but it is not likely a significant mechanism behind HAAF due to the supercompensation subsiding at 27 hours following the hypoglycemic episodes. In regard to memory and learning, brain glycogen is not required for motor skill learning while euglycemic, however, it does enhance motor memory while hypoglycemic as determined using a rotarod treadmill in mouse. In regard to associative learning, brain glycogen is important for contextual, but not cued, memories while both euglycemic and hypoglycemic, as assessed by contextual and cued fear conditioning. Two different genetically engineered models of mice lacking brain glycogen yielded opposing results when assessing whether brain glycogen is neuroprotective during severe and prolonged hypoglycemia. In conclusion, brain glycogen does not appear to play a role in HAAF, is important for learning and memory, and its role in neuronal cell survival during hypoglycemia requires further study. / Department of Biology

The present work was done to determine the effect of temperature of the half-saturation constant (ø) and the maximum transport rate (K) of the facilitated diffusion of glycerol across the erythrocyte membrane of Peromyscus californicus.

In 1938, Jacobs, et al. discussed differences in the permeability of the erythrocytes of rat and mouse to erythritol, mannitol, glycerol, and thiourea. Rat erythrocytes were more permeable to glycerol than to thiourea, whereas the reverse was true for mouse erythrocytes. Mouse erythrocytes also displayed a high degree of permeability to erythritol. However, this same substance penetrated rat cells much more slowly. Small but recognizable permeability differences were soo demonstrated among a number of species within a single genus. Levine (1943) investigated species differences in rates of osmotic hemolysis within the genus Peromyscus. The four species studied were: P. eremicus fraterculus, P. leucopus noveboracensis, P. gossypinus palmarius, and P. T. truei. Consistent differences in hemolysis times were demonstrated and it was possible to identify each species with certainty. Later experiments (LeFevre, 1948) suggested that glycerol and glucose did not enter the human red cell by simple diffusion, but rather that these penetrants were transported into the erythrocyte by an active metabolic system in which at least one essential link involved a sulfhydryl group Jacobs, et al. (1950) examined the inter-class erythrocyte permeabilities of mammals, birds, reptiles, amphibians, and fish to isosmotic solutions of urea, thiourea, glycerol, and ethylene glycol. Their results, which were generally consistent within a given class, indicated an unusually high permeability of glycerol and ethylene glycol in bird erythrocytes, and for urea in mammalian red cells. It was also found that the permeability of chicken red blood cells differed noticeably from the rather uniform pattern seen in the erythrocytes of such species as the pigeon, herring gull, English sparrow, pheasant, and turkey. In 1961, Hunter studied the effect of butanol on the permeability of human, rabbit, sheep, and chicken erythrocytes to glycerol, monoacetin, thiourea, and ammonium chloride. This work suggested that when the movement across the cell membrane depended on simple diffusion, butanol increased the permeability, but the effect of butanol on facilitated diffusion was inhibitory. A subsequent investigation by Hunter, George, and Ospina (1965) in which n-butyl alcohol and tannic acid were used, provided further help in distinguishing between simple and facilitated diffusion systems. This work suggested that a carrier system was present for glycerol in the erythrocytes of the rabbit, mouse, and man. During his study of hexose transport in beef erythrocytes, Laris (1967) noted considerable variation in the capacity of cells from different cattle to accumulate fructose both in the presence and in the absence of a metabolic inhibitor. Upon closer examination it was shown that beef erythrocytes could be divided into two distinct groups on the basis of differences in the fructose transport system. In a recent study, Hunger (1976) added six small mammals to the list of species in which a number of different nonelectrolytes penetrate the erythrocyte by facilitated diffusion. One of these six was the deer mouse (P. maniculatus), and it, like the other five species examined, was shown to have a carrier which is shared by glycerol and ethylene glycol. Hunger also obtained data which hinted at the possibility of permeability differences among separate populations of deer mice (Hunter, personal communication). Such findings prompted the present study of the permeability of red cells to glycerol in two different populations of the pinyon mouse (P. truei). In addition to this population comparison, the glycerol permeabilities of two closely related species, P. truei and P. californicus, were investigated

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Wu Yan. / "August 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 141-170). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy