title: Palmitoyl-CoA potentiates the Ca2+ release elicited by cyclic ADP-ribose.
abstract: Cyclic ADP-ribose (cADPR) is a potent mediator of Ca2+ mobilization from intracellular stores in sea urchin eggs that ultimately activates the ryanodine channel. We now report that certain long-chain acyl-CoA derivative metabolites (14-18 carbons in length), such as palmitoyl-CoA, greatly potentiate the effect of cADPR on Ca2+ release. Furthermore, in higher concentrations, palmitoyl-CoA and other closely related long-chain acyl-CoA derivatives trigger Ca2+ release apparently through the ryanodine channel in sea urchin egg homogenates. Palmitoyl-CoA-induced Ca2+ release was suppressed by ruthenium red, spermine, and the calmodulin antagonist N-(6-aminohexyl)-1-naphthalenesulfonamide, which all prevent activation of the ryanodine channel, but not by heparin or thionicotinamide-NADP. In addition, cADPR was able to desensitize the sea urchin egg homogenates to the subsequent Ca2+ release induced by palmitoyl-CoA and vice versa. In contrast, neither inositol 1,4,5-trisphosphate (IP3) nor the newly identified Ca2+ release agonist nicotinate adenine dinucleotide phosphate was able to desensitize the homogenate to palmitoyl-CoA, indicating that palmitoyl-CoA probably acts selectively by activating the ryanodine channel, but, unlike cADPR, palmitoyl-CoA might act directly on this channel. Finally, we found that palmitoyl-CoA was able to counteract the inhibitory effect of Mg2+ and spermine, which, in physiological concentrations, suppress specifically the cADPR-induced Ca2+ release. We propose that palmitoyl-CoA, present in micromolar concentrations, may trigger Ca2+ release through the ryanodine channel and, in lower concentrations, may increase the sensitivity of the Ca2+ release system to cADPR. Thus palmitoyl-CoA may serve as a regulatory link between the intermediary metabolism and the cADPR-induced Ca2+ release signaling pathway.
authors.affiliation: Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Chini
authors.forename: T P
authors.initials: TP
authors.lastname: Dousa
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D036563:Cyclic ADP-Ribose; D004357:Drug Synergism; D008274:Magnesium / Q000494:pharmacology; D009124:Muscle Proteins / Q000378:metabolism; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology*; D019837:Ryanodine Receptor Calcium Release Channel; D012617:Sea Urchins / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D036563:Cyclic ADP-Ribose; D010171:Palmitoyl Coenzyme A; D000246:Adenosine Diphosphate Ribose; D013096:Spermine; D008274:Magnesium; D002118:Calcium