Thesis (Ph. D.)--University of Wisconsin--Madison, 1960. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 71-75).

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (M. Med. Sc.)--University of Hong Kong, 2005.

Thesis (Ph. D.)--University of Idaho, 2005. / Abstract. "August 23, 2005." Includes bibliographical references. Also available online in PDF format.

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Hypertension affects 1 billion individuals worldwide and is the major contributing factor to cardiovascular disease. However, the WHO considers current antihypertensive drug therapies inadequate, highlighting a need for a novel approach to hypertension management. Baroreceptors are a promising drug target, and express an unusual glutamate receptor coupled to phospholipase D (PLD-GluR). The PLD-GluR has not been isolated and characterised, which is an important step towards its use as a drug target. A good source of the PLD-GluR is muscle spindle primary afferent nerve terminals, the largest mechanoreceptor in the body. This study thus focuses upon the identification and progress towards isolation of the PLD-GluR from muscle spindle primary afferent nerve terminals. A novel dissection method for high yield extraction of muscle spindles from a high density source, the rat deep masseter muscle, was developed for Western blotting and mass spectrometry screens of all GluRs. Western blots showed spindle homogenate contained a low molecular weight mGluR5 isoform and GluK2. Immunofluorescence showed mGluR5 was expressed on putative nociceptors, not mechanosensory nerve terminals. However, spindle mechanosensory nerve terminals labelled brightly for GluK2, as did baroreceptor nerve terminals. Furthermore, GluK2 appears to be the only GluR subunit on these mechanoreceptors, although mass spectrometry and affinity chromatography could not successfully isolate this receptor. Finally, piezo2 has recently been suggested as the major mechanotransducer protein. However, no evidence was found for piezo2 expression in adult spindle mechanosensory nerve terminals in adult rats or mice. As previous studies have largely focussed on adolescent mice, this could represent a developmental difference. Conversely, a number of candidate mechanosensory proteins, such as TRPs, were identified by a targeted mass spectrometry approach. This provides good candidates for future research. Collectively, this study indicates both spindle and baroreceptor mechanosensory nerve terminals express GluK2, suggesting it is at least a component of the PLD-GluR, and therefore potentially represents a novel drug target for treating hypertension.

No description available.

No description available.

Brain glutamic acid decarboxylase 65 (GAD65) catalyzes the rate-limiting step in the biosynthesis of the major inhibitory neurotransmitter-amino butyric acid (GABA) from the substrate L-glutamic acid. Severe lapse in GABA neurotransmission is one of the etiologies documented in the manifestation of certain neurodegenerative diseases such as epilepsy, Parkinson's disease, Huntington's disease etc. Because GAD65 synthesizes GABA, any modulation of GAD65, therefore, has direct implications on the quanta of GABA released at the synapse. Hence, the major objective of this study was to focus on the regulation of GAD65, with special emphasis on investigating the proteolytic cleavage of fGAD65. Previously, we have shown in vitro that GAD65 was cleaved to form its truncated form (tGAD65), which was more active than the full length form (fGAD65). The enzyme responsible for cleavage was later identified as calpain. Calpain is known to cleave its substrates either under a transient physiologica l stimulus or upon a sustained pathological insult. However, the precise role of calpain cleavage of fGAD65 is poorly understood. In this study, we examined the cleavage of fGAD65 under a range of conditions encompassing both physiological and pathological aspects, including rats under ischemia/reperfusion insult, rat brain synaptosomes or primary neuronal cultures subjected to excitotoxic stimulation with KCl. It was observed that the formation of tGAD65 progressively increased with increasing stimulus concentration. More importantly, cleavage of synaptic vesicle (SV) - associated fGAD65 by calpain was demonstrated, and the resulting tGAD65 harboring the active site of the enzyme was detached from the SVs. Vesicular uptake of the newly synthesized GABA into the SVs was found to be reduced in calpain treated SVs. Furthermore, we also observed that the levels of tGAD65 in the focal cerebral ischemic rat brain tissue increased corresponding to the elevation of local glutamate indica / d by in vivo micro dialysis. Based on these observations, we conclude that calpain cleavage of fGAD65 occurs under pathological conditions. / by Chandana Buddhala. / Thesis (Ph.D.)--Florida Atlantic University, 2012. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2012. Mode of access: World Wide Web.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves [95]-100).