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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/F341    most recent 00190.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Odgaard, E. Articles by Leipziger, J. PubMed PubMed Citation Articles by Odgaard, E. Articles by Leipziger, J.

AVP-stimulated nucleotide secretion in perfused mouse medullary thick ascending limb and cortical collecting duct

Department of Physiology and Biophysics, The Water and Salt Research Center, Aarhus University, Aarhus C, Denmark

Submitted 3 April 2009 ; accepted in final form 9 June 2009

Extracellular nucleotides are local, short-lived signaling molecules that inhibit renal tubular transport via both luminal and basolateral P2 receptors. Apparently, the renal epithelium itself is able to release nucleotides. The mechanism and circumstances under which nucleotide release is stimulated remain elusive. Here, we investigate the phenomenon of nucleotide secretion in intact, perfused mouse medullary thick ascending limb (mTAL) and cortical collecting duct (CCD). The nucleotide secretion was monitored by a biosensor adapted to register nucleotides in the tubular outflow. Intracellular Ca²⁺ concentration ([Ca²⁺]_i) was measured simultaneously in the biosensor cells and the renal tubule with fluo 4. We were able to identify spontaneous tubular nucleotide secretion in resting perfused mTAL. In this preparation, 10 nM AVP and 1-desamino-8-D-arginine vasopressin (dDAVP) induced robust [Ca²⁺]_i oscillations, whereas AVP in the CCD induced large, slow, and transient [Ca²⁺]_i elevations. Importantly, we identify that AVP/dDAVP triggers tubular secretion of nucleotides in the mTAL. After addition of AVP/dDAVP, the biosensor registered bursts of nucleotides in the tubular perfusate, corresponding to a tubular nucleotide concentration of 0.2–0.3 µM. A very similar response was observed after AVP stimulation of CCDs. Thus AVP stimulated tubular secretion of nucleotides in a burst-like pattern with peak tubular nucleotide concentrations in the low-micromolar range. We speculate that local nucleotide signaling is an intrinsic feedback element of hormonal control of renal tubular transport.

ATP release; renal tubule; vasopressin; purinergic