New Ca2+-releasing messengers: are they important in the nervous system?

In the nervous system, Ca2+ signalling is determined primarily by voltage-g ated Ca2+-selective channels in the plasma membrane, but there is increasin g evidence for involvement of intracellular Ca2+ stores in such signalling. It is generally assumed that neurotransmitter-elicited release of Ca2+ fro m internal stores is primarily mediated by Ins(1,4,5)P-3, as originally dis covered in pancreatic acinar cells. The more-recently discovered Ca2+-relea sing messenger, cyclic ADP-ribose (cADPR), which activates ryanodine recept ors, has so far only been implicated in a few cases, and the possible impor tance of another Ca2+-releasing molecule, nicotinic acid adenine dinucleoti de phosphate (NAADP), has been ignored. Recent investigations of the action of the brain-gut peptide cholecystokinin on pancreatic acinar cells have i ndicated that NAADP and cADPR receptors are essential for Ca2+ release. Too ls are available for testing the possible involvement of NAADP and cADPR in neurotransmitter-elicited intracellular Ca2+ release, and such studies cou ld reveal complex mechanisms that control this release in the nervous syste m.