Catalytic properties of the retinal rod outer segment disk ADP-ribosyl cyclase

Vis Neurosci. 2011 Mar;28(2):121-8. doi: 10.1017/S0952523810000404. Epub 2011 Jan 27.


Cyclic ADP-ribose (cADPR) is a second messenger modulating intracellular calcium levels. We have previously described a cADPR-dependent calcium signaling pathway in bovine rod outer segments (ROS), where calcium ions play a pivotal role. ROS ADP-ribosyl cyclase (ADPR-cyclase) was localized in the membrane fraction. In the present work, we examined the properties of the disk ADPR-cyclase through the production of cyclic GDP-ribose from the NAD(+) analogue NGD(+). The enzyme displayed an estimated K(m) for NGD(+) of 12.5 ± 0.3 μM, a V(max) of 26.50 ± 0.70 pmol cyclic GDP-ribose synthesized/min/mg, and optimal pH of 6.5. The effect of divalent cations (Zn(2+), Cu(2+), and Ca(2+)) was also tested. Micromolar Zn(2+) and Cu(2+) inhibited the disk ADPR-cyclase activity (half maximal inhibitory concentration, IC50=1.1 and 3.6 μM, respectively). By contrast, Ca(2+) ions had no effect. Interestingly, the properties of the intracellular membrane-associated ROS disk ADPR-cyclase are more similar to those of the ADPR-cyclase found in CD38-deficient mouse brain, than to those of CD38 or CD157. The novel intracellular mammalian ADPR-cyclase would elicit Ca(2+) release from the disks at various rates in response to change in free Ca(2+) concentrations, caused by light versus dark adaptation, in fact there was no difference in disk ADPR-cyclase activity in light or dark conditions. Data suggest that disk ADPR-cyclase may be a potential target of retinal toxicity of Zn(2+) and may shed light to the role of Cu(2+) and Zn(2+) deficiency in retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase / metabolism*
  • Animals
  • Calcium / pharmacology
  • Cattle
  • Copper / pharmacology
  • Dose-Response Relationship, Drug
  • Guanine Nucleotides / metabolism
  • Microscopy, Electron, Transmission / methods
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / ultrastructure
  • NAD / analogs & derivatives
  • NAD / metabolism
  • Osmolar Concentration
  • Photic Stimulation
  • Retina / cytology*
  • Retinal Rod Photoreceptor Cells / cytology*
  • Rhodopsin / metabolism
  • Rod Cell Outer Segment / drug effects
  • Rod Cell Outer Segment / enzymology*
  • Rod Cell Outer Segment / ultrastructure
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Zinc / pharmacology


  • Guanine Nucleotides
  • NAD
  • nicotinamide guanine dinucleotide
  • Copper
  • Rhodopsin
  • ADP-ribosyl Cyclase
  • Sodium-Potassium-Exchanging ATPase
  • Zinc
  • Calcium