title: Elucidation of the ryanodine-sensitive Ca2+ release mechanism of rat pancreatic acinar cells: modulation by cyclic ADP-ribose and FK506.
abstract: The effects of cyclic ADP-ribose (cADPR) and the immunosuppressant drug FK506 on microsomal Ca2+ release through a ryanodine-sensitive mechanism were investigated in rat pancreatic acinar cells. After a steady state of 45Ca2+ uptake into the microsomal vesicles, ryanodine or caffeine was added. Preincubation of the vesicles with cADPR (0.5 microM) shifted the dose-response curve of ryanodine- or caffeine-induced 45Ca2+ release from the vesicles to the left. Preincubation with cADPR shifted the dose-response curve of the FK506-induced 45Ca2+ release upward. Preincubation with FK506 (3 microM) shifted the dose-response curve of the ryanodine- or caffeine-induced 45Ca2+ release to the left by the same extent as that in the case of cADPR. FK506 shifted the dose-response curve of the cADPR-induced 45Ca2+ release upward. The presence of both cADPR and FK506 enhanced the ryanodine (30 microM)- or caffeine (10 mM)-induced 45Ca2+ release by the same extent as that in the case of cADPR alone or FK506 alone. These results indicate that cADPR and FK506 modulate the ryanodine-sensitive Ca2+ release mechanism of rat pancreatic acinar cells by increasing the ryanodine or caffeine sensitivity to the mechanism. In addition, there is a possibility that the mechanisms of modulation by cADPR and FK506 are the same.
authors.affiliation: Department of Physiology, Graduate School of Medicine, Tohoku University, Seiryo-machi 2-1, Aoba-ku, Sendai 980-8575, Japan. teozawa@mail.tains.tohoku.ac.jp
authors.forename: Terutaka
authors.initials: T
authors.lastname: Ozawa
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D000246:Adenosine Diphosphate Ribose; D002110:Caffeine; D002118:Calcium; D016559:Tacrolimus