title: Cyclic ADP-ribose, the ADP-ribosyl cyclase pathway and calcium signalling.
abstract: Cyclic adenosine diphosphate-ribose, an endogenous metabolite of nicotinamide adenine dinucleotide was first characterized as a potent Ca2+ mobilizing agent in sea urchin eggs. Mounting evidence points to it being an endogenous activator of Ca(2+)-induced Ca2+ release by non-skeletal muscle ryanodine receptors in several invertebrate and mammalian cell types. Cyclic adenosine diphosphate-ribose is synthesized by adenosine diphosphate-ribosyl cyclases, which have been found to be widespread enzymes. Recent data suggests that cyclic adenosine diphosphate-ribose may function as a second messenger in sea urchin eggs at fertilization and in stimulus secretion coupling in pancreatic beta-cells. A second messenger role for cyclic adenosine diphosphate-ribose requires that its intracellular levels be under the control of extracellular stimuli. Another second messenger, cGMP, stimulates the synthesis of cyclic adenosine diphosphate-ribose from nicotinamide adenine dinucleotide by activating the adenosine diphosphate-ribosyl cyclase pathway in sera urchin eggs and egg homogenates, suggesting that cyclic adenosine diphosphate-ribose may be an intracellular messenger for cell surface receptors or nitric oxide, which activate cGMP-producing guanylate cyclases. Cyclic adenosine diphosphate-ribose may have a similar role to inositol trisphosphate in controlling intracellular calcium signalling with these two calcium-mobilizing second messengers activating ryanodine receptors and inositol trisphosphate receptors respectively.
authors.affiliation: Department of Pharmacology, Oxford University, UK.
authors.forename: A
authors.initials: A
authors.lastname: Galione
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000502:physiology; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D036563:Cyclic ADP-Ribose; D009124:Muscle Proteins / Q000502:physiology; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015220:Calcium Channels; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium