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The studies described in this thesis have used principally the rat neonatal cardiomyocyte (NCM) model to investigate previously unresolved questions regarding inositol phosphate signalling in the heart. Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) is known to be an arrhythmogenic molecule in the setting of cardiacischaemia and subsequent reperfusion, but the mechanisms responsible for its enhanced generation in pathological circumstances, as well as those suppressing its generation during phospholipase C (PLC)-coupled receptor stimulation under physiological conditions, have not been characterised. [3H]Inositol-labelling in combination with anion-exchange high performance liquid chromatography (HPLC)was used to gain an accurate picture of the changes in various [3H]InsP isomers induced by PLC stimulation.

Bibliography: leaves 151-184 / vi, 184 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Botany, 1990

Indiana University-Purdue University Indianapolis (IUPUI) / FGF23 is the central regulator for phosphate homeostasis. Both FGF23 and phosphate dysregulation are highly related with the progression of chronic kidney disease (CKD), which is a global health problem. In previous studies, FGF23 was found to be produced in bone and targeting the kidneys to regulate phosphate reabsorption and excretion. In the FGF23 signaling axis, it binds a receptor complex (αKlotho and FGFRs) in the distal convoluted tubules (DCT) and causes its biological effects in the proximal tubules (PT). The mechanism of how the signals passing on from DCT to PT is not clear. In my research, experiments were focused on the FGF23 signaling pathway within the kidney to study the communication steps between tubular cells. HBEGF treatment was given to FGF23 signaling impaired mouse models resulting in significant change of genes regulated by FGF23, indicating that HBEGF was important in the FGF23 signaling axis. Then high quality rabbit anti-mouse HBEGF antibodies were made to better study HBEGF activity in vivo and in vitro. A new cell model was characterized to test FGF23 effects on HBEGF signaling using Western blots and immunofluorescence. Lastly, the location of HBEGF activity was examined in the kidney in vivo. Immunostaining suggested that HBEGF activated the mitogen activated protein kinase (MAPK) pathway. This mapping may provide important information for the molecular relationships between FGF23 and HBEGF.