HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/F510    most recent 00116.2009v1 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 Thai, T. L. Articles by Arendshorst, W. J. PubMed PubMed Citation Articles by Thai, T. L. Articles by Arendshorst, W. J.

NAADP receptors mediate calcium signaling stimulated by endothelin-1 and norepinephrine in renal afferent arterioles

¹Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and ²Department of Pharmacology, Oxford University, Oxford, United Kingdom

Submitted 27 February 2009 ; accepted in final form 12 May 2009

The enzyme ADP-ribosyl (ADPR) cyclase plays a significant role in mediating increases in renal afferent arteriolar cytosolic calcium concentration ([Ca²⁺]_i) in vitro and renal vasoconstriction in vivo. ADPR cyclase produces cyclic ADP ribose, a second messenger that contributes importantly to ryanodine receptor-mediated Ca²⁺ mobilization in renal vascular responses to several vasoconstrictors. Recent studies in nonrenal vascular smooth muscle cells (VSMC) have shown that nicotinic acid adenine dinucleotide phosphate (NAADP), another second messenger generated by ADPR cyclase, may contribute to Ca²⁺ signaling. We tested the hypothesis that a Ca²⁺ signaling pathway involving NAADP receptors participates in afferent arteriolar [Ca²⁺]_i responses to the G protein-coupled receptor agonists endothelin-1 (ET-1) and norepinephrine (NE). To test this, we isolated rat renal afferent arterioles and measured [Ca²⁺]_I using fura-2 fluorescence. We compared peak [Ca²⁺]_i increases stimulated by ET-1 and NE in the presence and absence of inhibitors of acidic organelle-dependent Ca²⁺ signaling and NAADP receptors. Vacuolar H⁺-ATPase inhibitors bafilomycin A1 and concanamycin A, disruptors of pH and Ca²⁺ stores of lysosomes and other acidic organelles, individually antagonized [Ca²⁺]_i responses to ET-1 and NE by 40–50% (P < 0.05). The recently discovered NAADP receptor inhibitor Ned-19 attenuated [Ca²⁺]_i responses to ET-1 or NE by 60–70% (P < 0.05). We conclude that NAADP receptors contribute to both ET-1- and NE-induced [Ca²⁺]_i responses in afferent arterioles, an effect likely dependent on acidic vesicle, possibly involving lysosome, signaling in VSMC in the renal microcirculation.

adenosine 5'-diphosphate-ribosyl cyclase; calcium mobilization; vascular smooth muscle cells; renal circulation