Cyclic ADP-ribose activates caffeine-sensitive calcium channels from sea urchin egg microsomes.
Adenosine 5'-cyclic diphosphoribose [cyclic ADP-ribose (cADPR)], a metabolite of NAD+ that promotes Ca2+ release from sea urchin egg homogenates and microsomal fractions, has been proposed to act as an endogenous agonist of Ca2+ release in sea urchin eggs. We describe experiments showing that a microsomal fraction isolated from Tetrapigus nyger sea urchin eggs displayed Ca(2+)-selective single channels with conductances of 155.0 +/- 8.0 pS in asymmetric Cs+ solutions and 47.5 +/- 1.1 pS in asymmetric Ca2+ solutions. These channels were sensitive to stimulation by Ca2+, ATP, and caffeine, but not inositol 1,4,5-trisphosphate, and were inhibited by ruthenium red. The channels were also activated by cADP-ribose in a Ca(2+)-dependent fashion. Calmodulin and Mg2+, but not heparin, modulated channel activity in the presence of cADP-ribose. We propose that these Ca2+ channels constitute the intracellular Ca(2+)-induced Ca2+ release pathway that is activated by cADP-ribose in sea urchin eggs.
Pérez
C F
CF
Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Marengo
J J
JJ
Bull
R
R
Hidalgo
C
C
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D036563:Cyclic ADP-Ribose; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D007202:Indicators and Reagents / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008051:Lipid Bilayers / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D010063:Ovum / Q000187:drug effects / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology; D012617:Sea Urchins; D013449:Sulfonamides / Q000494:pharmacology
D015220:Calcium Channels; D002147:Calmodulin; D007202:Indicators and Reagents; D008051:Lipid Bilayers; D013449:Sulfonamides; D012430:Ruthenium Red; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D002110:Caffeine; C017967:W 7; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D008274:Magnesium; D002118:Calcium