TY - JOUR
T1 - Cyclic ADP-ribose metabolism in rat kidney
T2 - High capacity for synthesis in glomeruli
AU - Chini, E. N.
AU - Klener P., Jr
AU - Beers, K. W.
AU - Chini, C. C.S.
AU - Grande, J. P.
AU - Dousa, T. P.
N1 - Funding Information:
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-16105, Grant DK-30795 (T.P.D.), Grant DK-45280 (J.P.G.) and by the Mayo Foundation. Dr. EN. Chini is a Research Fellow at the National Kidney Foundation and Dr.
PY - 1997
Y1 - 1997
N2 - Recent discovery of cyclic ADP-ribose (cADPR) as an agent that triggers Ca2+ release from intracellular stores, through ryanodine receptor channel, is an important new development in the investigation of intracellular signaling mechanisms. We determined the capacity of kidney and its components for synthesis of cADPR from β-NAD, that is catalyzed by enzyme ADP-ribosyl cyclase, and enzymatic inactivation that is catalyzed by cADPR- glycohydrolase. Little or no activity of ADP-ribosyl cyclase was found in extracts from the whole rat kidney, renal cortex, outer and inner medulla. On the other hand, incubation of β-NAD with similar extracts from rat liver, spleen, heart, and brain resulted in biosynthesis of cADPR. In addition, extracts from suspension of proximal tubules or microdissected proximal convoluted tubules virtually lacked ADP-ribosyl cyclase activity. In sharp contrast to proximal tubules and cortex, extracts from glomeruli had high ADP-ribosyl cyclase activity, similar to that found in non-renal tissues. Authenticity of cADPR biosynthesized in glomeruli was documented by several criteria such as HPLC analysis, effect of inhibitors and homologous desensitization of Ca2+-release bioassay. On the other hand, the activity of cADPR-glycohydrolase was similar in extracts from glomeruli and in extracts from kidney cortex. Mesangial cells and vascular smooth muscle cells grown in primary culture displayed considerable ADPR-ribose cyclase activity. Our results show that extracts from glomeruli, unlike extracts from renal tissue zones and proximal tubules, have a singularly high capacity for synthesis of cADPR. We surmise that cADPR-triggered Ca2+-releasing system can serve as an intracellular signaling pathway that may be operant in regulations of glomerular cell functions.
AB - Recent discovery of cyclic ADP-ribose (cADPR) as an agent that triggers Ca2+ release from intracellular stores, through ryanodine receptor channel, is an important new development in the investigation of intracellular signaling mechanisms. We determined the capacity of kidney and its components for synthesis of cADPR from β-NAD, that is catalyzed by enzyme ADP-ribosyl cyclase, and enzymatic inactivation that is catalyzed by cADPR- glycohydrolase. Little or no activity of ADP-ribosyl cyclase was found in extracts from the whole rat kidney, renal cortex, outer and inner medulla. On the other hand, incubation of β-NAD with similar extracts from rat liver, spleen, heart, and brain resulted in biosynthesis of cADPR. In addition, extracts from suspension of proximal tubules or microdissected proximal convoluted tubules virtually lacked ADP-ribosyl cyclase activity. In sharp contrast to proximal tubules and cortex, extracts from glomeruli had high ADP-ribosyl cyclase activity, similar to that found in non-renal tissues. Authenticity of cADPR biosynthesized in glomeruli was documented by several criteria such as HPLC analysis, effect of inhibitors and homologous desensitization of Ca2+-release bioassay. On the other hand, the activity of cADPR-glycohydrolase was similar in extracts from glomeruli and in extracts from kidney cortex. Mesangial cells and vascular smooth muscle cells grown in primary culture displayed considerable ADPR-ribose cyclase activity. Our results show that extracts from glomeruli, unlike extracts from renal tissue zones and proximal tubules, have a singularly high capacity for synthesis of cADPR. We surmise that cADPR-triggered Ca2+-releasing system can serve as an intracellular signaling pathway that may be operant in regulations of glomerular cell functions.
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U2 - 10.1038/ki.1997.206
DO - 10.1038/ki.1997.206
M3 - Article
C2 - 9150465
AN - SCOPUS:0031004209
SN - 0085-2538
VL - 51
SP - 1500
EP - 1506
JO - Kidney international
JF - Kidney international
IS - 5
ER -