title: Cyclic ADP-ribose induces Ca2+ release from caffeine-insensitive Ca2+ pools in canine salivary gland cells.
abstract: Cyclic ADP-ribose (cADPR), a novel putative messenger of the ryanodine receptor, was examined regarding its ability to mobilize Ca2+ from intracellular Ca2+ stores in isolated cells of parotid and submandibular glands of the dog. cADPR induced a rapid and transient Ca2+ release in the digitonin-permeabilized cells of salivary glands. cADPR-induced Ca2+ release was inhibited by ryanodine receptor antagonists ruthenium red, ryanodine, benzocaine, and imperatoxin inhibitor but not by the inositol 1,4,5-trisphosphate (IP3)-receptor antagonist heparin. Thapsigargin, at a concentration of 3 to 30 microM, inhibited IP3-induced Ca2+ release, while higher concentrations were required to inhibit cADPR-induced Ca2+ release. Cross-potentiation was observed between cADPR and ryanodine or SrCl2, suggesting that cADPR sensitizes the Ca2+-induced Ca2+ release mechanism. Cyclic AMP plays a stimulatory role on cADPR- and IP3-induced Ca2+ release in digitonin-permeabilized cells. Calmodulin also potentiated cADPR-induced Ca2+ release, but inhibited IP3-induced Ca2+ release. Acetylcholine and ryanodine caused the rise in intracellular free Ca2+ concentration ([Ca2+]i) in intact submandibular and parotid cells. Caffeine did not produce any increase in Ca2+ release or [Ca2+]i rise in any preparation. ADP-ribosyl cyclase activity was found in the centrifuged particulate fractions of the salivary glands. These results suggest that cADPR serves as an endogenous modulator of Ca2+ release from Ca2+ pools through a caffeine-insensitive ryanodine receptor channel, which are different from IP3-sensitive pools in canine salivary gland cells. This system is positively regulated by cyclic AMP and calmodulin.
authors.affiliation: Department of Removable Prosthodontics, Hiroshima University School of Dentistry, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamaki
authors.forename: K
authors.initials: K
authors.lastname: Morita
authors.forename: S
authors.initials: S
authors.lastname: Kitayama
authors.forename: Y
authors.initials: Y
authors.lastname: Imai
authors.forename: K
authors.initials: K
authors.lastname: Itadani
authors.forename: Y
authors.initials: Y
authors.lastname: Akagawa
authors.forename: T
authors.initials: T
authors.lastname: Dohi
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D036563:Cyclic ADP-Ribose; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009097:Multienzyme Complexes / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D009244:NAD+ Nucleosidase / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D009097:Multienzyme Complexes; D010726:Phosphodiesterase Inhibitors; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D002110:Caffeine; D036541:ADP-ribosyl Cyclase; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium