title: Cyclic ADP-ribose metabolism in rat kidney: high capacity for synthesis in glomeruli.
abstract: 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 beta-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 beta-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 Ca(2+)-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 Ca(2+)-releasing system can serve as an intracellular signaling pathway that may be operant in regulations of glomerular cell functions.
authors.affiliation: Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Chini
authors.forename: P
authors.initials: P
authors.lastname: Klener
authors.forename: K W
authors.initials: KW
authors.lastname: Beers
authors.forename: C C
authors.initials: CC
authors.lastname: Chini
authors.forename: J P
authors.initials: JP
authors.lastname: Grande
authors.forename: T P
authors.initials: TP
authors.lastname: Dousa
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D036563:Cyclic ADP-Ribose; D007668:Kidney / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D002118:Calcium