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Cyclic ADP-ribose Induces Ca2+ Release from Caffeine-insensitive Ca2+ Pools in Canine Salivary Gland Cells
H. Yamaki
Department of Removable Prosthodontics
K. Morita
Department of Pharmacology, Hiroshima University School of Dentistry, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan
S. Kitayama
Department of Pharmacology, Hiroshima University School of Dentistry, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan
Y. Imai
Department of Pharmacology, Hiroshima University School of Dentistry, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan
K. Itadani
Department of Removable Prosthodontics
Y. Akagawa
Department of Removable Prosthodontics
T. Dohi
Department of Pharmacology, Hiroshima University School of Dentistry, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan
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 (IP 3)-receptor antagonist heparin. Thapsigargin, at a concentration of 3 to 30 µM, 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 [Ca 2+]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 Ca 2+ 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.
Key Words: cyclic ADP-ribose parotid gland submandibular gland calcium caffeine.
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Journal of Dental Research, Vol. 77, No. 10,
1807-1816 (1998)
DOI: 10.1177/00220345980770100801

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