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dc.contributor.advisorAiton, Jim
dc.contributor.advisorCramb, Gordon
dc.contributor.authorRugg, Elizabeth Louise
dc.coverage.spatial[ca 250] p.en_US
dc.description.abstractAtrial natriuretic peptide (ANP) has previously been shown to increase intracellular cGMP levels in isolated rat ventricular myocytes. Using purified rat cardiac sarcolemmal membranes, a series of experiments was performed to investigate the mechanisms by which this occurs. A second series of experiments was carried out to investigate the nature of ANP degradation by preparations isolated from rat heart, lung and kidney. In rat cardiac sarcolemmal membranes, ANP produced a 1.8-fold stimulation of manganese-dependent guanylate cyclase activity, with a Km of around 1nM. This activity was attenuated by the presence of 1 nM ATP in the incubation. In the presence of magnesium, guanylate cyclase activity was reduced 20- to 40-fold, but was augmented by ATP. Similar results were obtained in the presence of ANP-PNP, a non-hydrolysable analogue of ATP. [125I]-ANP binding studies indicated the presence of two receptor/affinity states, with KD'S of less than 10 pM, and around 1 nM for the high and low affinity sites respectively. More than 90% of these receptors were of the low affinity form. Similar results were obtained with bovine adrenal cortex membranes, but with MDCK cell membranes, only high affinity binding sites could be detected. These experiments indicate that rat cardiac sarcolemmal membranes possess ANP receptors, at least a proportion of which are coupled to guanylate cyclase. Incubation of [125I]-ANP with isolated rat ventricular myocytes, or with a cytosolic fraction prepared from these cells, resulted in its rapid degradation. The proteolytic activity appeared to be due to the action of a soluble metallopeptidase. Incubation of [125I]-ANP with a cytosolic fraction prepared from rat kidney and lung indicated that similar degradative activity could be isolated from these tissues.en_US
dc.publisherUniversity of St Andrews
dc.titleBiochemical actions and degradations of atrial natriuretic peptide in rat tissuesen_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US

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