Hypotonicity-induced Renin exocytosis from juxtaglomerular cells requires aquaporin-1 and cyclooxygenase-2.
The mechanism by which extracellular hypotonicity stimulates release of renin from juxtaglomerular (JG) cells is unknown. We hypothesized that osmotically induced renin release depends on water movement through aquaporin-1 (AQP1) water channels and subsequent prostanoid formation. We recorded membrane capacitance (C(m)) by whole-cell patch clamp in single JG cells as an index of exocytosis. Hypotonicity increased C(m) significantly and enhanced outward current. Indomethacin, PLA(2) inhibition, and an antagonist of prostaglandin transport impaired the C(m) and current responses to hypotonicity. Hypotonicity also increased exocytosis as determined by a decrease in single JG cell quinacrine fluorescence in an indomethacin-sensitive manner. In single JG cells from COX-2(-/ -) and AQP1(-/ -) mice, hypotonicity increased neither C(m) nor outward current, but 0.1-muM PGE(2) increased both in these cells. A reduction in osmolality enhanced cAMP accumulation in JG cells but not in renin-producing As4.1 cells; only the former had detectable AQP1 expression. Inhibition of protein kinase A blocked the hypotonicity-induced C(m) and current response in JG cells. Taken together, our results show that a 5 to 7% decrease in extracellular tonicity leads to AQP1-mediated water influx in JG cells, PLA(2)/COX-2-mediated prostaglandin-dependent formation of cAMP, and activation of PKA, which promotes exocytosis of renin.
Friis
Ulla G
UG
Department of Physiology and Pharmacology, Institute of Medical Biology, University of Southern Denmark, DK-5000 Odense, Denmark. ufriis@health.sdu.dk
Madsen
Kirsten
K
Svenningsen
Per
P
Hansen
Pernille B L
PB
Gulaveerasingam
Ambika
A
Jørgensen
Finn
F
Aalkjaer
Christian
C
Skøtt
Ole
O
Jensen
Boye L
BL
D000818:Animals; D051398:Aquaporin 1 / Q000502:physiology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000502:physiology*; D005089:Exocytosis; D007038:Hypotonic Solutions; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009994:Osmolar Concentration; D054467:Phospholipases A2 / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*
C496021:Aqp1 protein, mouse; C496022:Aqp1 protein, rat; D007038:Hypotonic Solutions; D051398:Aquaporin 1; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; D054467:Phospholipases A2; D012083:Renin