Premium
Amplification of depolarization‐induced and ryanodine‐sensitive cytosolic Ca 2+ elevation by synthetic carbocyclic analogs of cyclic ADP‐ribose and their antagonistic effects in NG108‐15 neuronal cells
Author(s) -
Hashii Minako,
Shuto Satoshi,
Fukuoka Masayoshi,
Kudoh Takashi,
Matsuda Akira,
Higashida Haruhiro
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03197.x
Subject(s) - cyclic adp ribose , depolarization , ryanodine receptor , membrane potential , chemistry , biophysics , second messenger system , ribose , stereochemistry , biochemistry , receptor , biology , microbiology and biotechnology , cd38 , stem cell , cd34 , enzyme
We synthesized analogs modified in the ribose unit (ribose linked to N1 of adenine) of cyclic ADP‐ribose (cADPR), a Ca 2+ ‐mobilizing second messenger. The biological activities of these analogs were determined in NG108‐15 neuroblastoma × glioma hybrid cells that were pre‐loaded with fura‐2 acetoxymethylester and subjected to whole‐cell patch‐clamp. Application of the hydrolysis‐resistant cyclic ADP‐carbocyclic‐ribose (cADPcR) through patch pipettes potentiated elevation of the cytoplasmic free Ca 2+ concentration ([Ca 2+ ] i ) at the depolarized membrane potential. The increase in [Ca 2+ ] i evoked upon sustained membrane depolarization was significantly larger in cADPcR‐infused cells than in non‐infused cells and its degree was equivalent to or significantly greater than that induced by cADPR or β‐NAD + . 8‐chloro‐cADPcR and two inosine congeners (cyclic IDP‐carbocyclic‐ribose and 8‐bromo‐cyclic IDP‐carbocyclic‐ribose) did not induce effects similar to those of cADPcR or cADPR. Instead, 8‐chloro‐cADPcR together with cADPR or cADPcR caused inhibition of the depolarization‐induced [Ca 2+ ] i increase as compared with either cADPR or cADPcR alone. These results demonstrated that our cADPR analogs have agonistic or antagonistic effects on the depolarization‐induced [Ca 2+ ] i increase and suggested the presence of functional reciprocal coupling between ryanodine receptors and voltage‐activated Ca 2+ channels via cADPR in mammalian neuronal cells.