Formation and actions of cyclic ADP-ribose in renal microvessels.
Recent studies indicated that cyclic ADP-ribose (cADPR) serves as a second messenger for intracellular Ca(2+) mobilization in a variety of mammalian cells. However, the metabolism and actions of cADPR in the renal vasculature are poorly understood. In the present study, we characterized the enzymatic pathway of the production and metabolism of cADPR along the renal vascular tree and determined the role of cADPR in the control of intracellular [Ca(2+)] and vascular tone. The high performance liquid chromatographic analyses showed that cADPR was produced and hydrolyzed along the renal vasculature. The maximal conversion rate of nicotinamide guanine dinucleotide (NGD) into cyclic GDP-ribose (that represents ADP-ribosyl cyclase activity for cADPR formation) was 8.69 +/- 2.39 nmol/min/mg protein in bulk-dissected intrarenal preglomerular vessels (n = 7) and 4.35 +/- 0.13, 2.23 +/- 0.27, 2.40 +/- 0.19, and 0.31 +/- 0.02 nmol/min/mg protein, respectively, in microdissected arcuate arteries (n = 6), interlobular arteries (n = 6), afferent arterioles (n = 7), and vasa recta (n = 10). The activity of cADPR hydrolase was also detected in the renal vasculature. Using the fluorescence microscopic spectrometry, cADPR was found to produce a large rapid Ca(2+) release from beta-escin-permeabilized renal arterial smooth muscle cells (SMCs). In isolated, perfused, and pressurized small renal arteries, cADPR produced a concentration-dependent vasoconstriction when added into the bath solution. The vasoconstrictor effect of cADPR was completely blocked by tetracaine, a Ca(2+)-induced Ca(2+) release (CICR) inhibitor. These results suggest that an enzymatic pathway for cADPR production and metabolism is present along the renal vasculature and that cADPR may importantly contribute to the control of renal vascular tone through CICR.
Li
N
N
Departments of Physiology and Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee 53226, USA.
Teggatz
E G
EG
Li
P L
PL
Allaire
R
R
Zou
A P
AP
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D036563:Cyclic ADP-Ribose; D007668:Kidney / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000502:physiology*
D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D002118:Calcium