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Spontaneous and stimulated nucleotide release from renal epithelia


Elvin V. P. Odgaard


The functional units of the kidney, the nephrons, serve the crucial role ofmaintaining an optimal body water and salt balance, in conjunction to theelimination of unwanted water soluble “waste” products. The epithelial transportof salt and water is a finely tuned and regulated process. The regulation oftransport has traditionally been viewed as a phenomenon orchestrated byhormones such as aldosterone, arginine-vasopressin (AVP) or angiotensin II.This research project is the summary of three original manuscripts addressing therole of an auto- and paracrine cellular communication system, using locallyreleased nucleotides (e.g. ATP) as a signalling molecule capable of regulatingwater and salt transport.The first paper addresses the phenomenon of spontaneous oscillatory [Ca2+]iincreases in isolated perfused and cultured kidney cells. The article shows howthese oscillations are the result of locally released nucleotides, which mediate P2receptor activation.The second paper investigates how changes in tubular flow in the isolatedperfused thick ascending limb provoke transient increases in [Ca2+]i and againshows how this cellular response is closely linked to local release of nucleotides.Finally, in the third manuscript we have established a method to directly sensereleased nucleotides in perfused renal tubules. We use this method to confirmthe phenomenon of spontaneous nucleotide release/secretion from intact isolatedrenal segments. Furthermore, we use this method to show that AVP is able toinduce a secretion of nucleotides from isolated perfused thick ascending limbsand cortical collecting ducts.