CALCIUM MOBILIZATION BY INOSITOL PHOSPHATES AND OTHER INTRACELLULAR MESSENGERS

Inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] is now widely recognized as a messenger controlling the release of calcium from intracellular s tores. In oocytes, and also probably in. excitable cells, another pote ntial calcium-mobilizing messenger is cyclic ADP ribose, although ther e is as yet little evidence that its levels are regulated by hormones or other extracellular mediators. In addition to signaling intracellul ar calcium release, [Ins(1,4,5)P-3] also regulates calcium entry acros s the plasma membrane, but not in a direct manner Rather the depletion of intracellular stores by the calcium-mobilizing action of [Ins(1,4, 5)P-3] initiates a process of retrograde signaling whereby the deplete d stoves generate or release a diffusible messenger that is believed t o act on the plasma membrane. A phosphorylated metabolite of [Ins(1,4, 5)P-3], inositol 1,3,4,5-tetrakisphosphate [Ins(1,3, 4, 5)P-4], has be en proposed to modulate this process, but the literature is not consis tent on this point. A recently proposed candidate for the retrograde m essenger is an activity extracted from Jurkat cells termed CIF (calciu m influx factor), which has many properties consistent with such a mes senger. There is also evidence that a GTP-dependent process, possibly involving a Small G protein, is involved in signaling calcium entry an d may be involved in either the formation or action of the diffusible messenger for calcium entry.