Intracellular Ca2+ release mechanisms: multiple pathways having multiple functions within the same cell type?

The elevation of the cytosolic and nuclear Ca2+ concentration is a fundamen tal signal transduction mechanism in almost all eukaryotic cells. Interesti ngly, three Ca2+-mobilising second messengers, D-myo-inositol 1,4,5-trispho sphate (InsP(3)), cyclic adenosine diphosphoribose (cADPR), and nicotinic a cid adenine dinucleotide phosphate (NAADP(+)) were identified in a phylogen etically wide range of different organisms. Moreover, in an as yet very lim ited number of cell types, sea urchin eggs, mouse pancreatic acinar cells, and human Jurkat T-lymphocytes, all three Ca2+-mobilising ligands have been shown to be involved in the generation of Ca2+ signals. This situation rai ses the question why during evolution all three messengers have been conser ved in the same cell type. From a theoretical point of view the following p oints may be considered: (i) redundant mechanisms ensuring intact Ca2+ sign alling even if one system does not work, (ii) the need for subcellularly lo calised Ca2+ elevations to obtain a certain physiological response of the c ell, and (iii) tight control of a physiological response of the cell by a t emporal sequence of Ca2+ signalling events. These theoretical consideration s are compared to the current knowledge regarding the three messengers in s ea urchin eggs, mouse pancreatic acinar cells, and human Jurkat T lymphocyt es. (C) 2000 Elsevier Science B.V. All rights reserved.