Palmitoyl-coa potentiates the ca2+ release elicited by cyclic adp -ribose. Chini, Eduardo N., and Thomas P. Dousa. Renal Pathophysiology LAboratory, Departments of Physiology, Biophysics, and Internal Medicine, Mayo Clinic and Foundation, Rochester, MN.
APStracts 2:0314C, 1995.
Cyclic ADP-ribose (cADPR) is a potent mediator of calcium 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 (C14-C18), such as palmitoyl -CoA, greatly potentiate the effect of cADPR upon 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 by the calmodulin antagonist W-7 (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 (NAADP) were 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 upon 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 trough the ryanodine channel and in lower concentrations 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. 

Received 4 May 1995; accepted in final form 21 August 1995.
APS Manuscript Number C244-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.