Role of nitric oxide and its intracellular signalling pathways in the control of Ca2+ homeostasis.
Ca2+, a primary regulator of physiological functions in all cells, is involved in a variety of intracellular signalling pathways; control of Ca2+ homeostasis is, therefore, a fundamental cell activity. To this end, cells have developed a variety of mechanisms to ensure the buffering of Ca2+, its influx and extrusion from the plasma membrane, and its release/accumulation within specific intracellular storage compartments. Over the last few years, evidence gathered from a number of cell systems has indicated that one of the key messengers governing the overall control of Ca2+ homeostasis is nitric oxide (NO), which may be produced intracellularly or may originate from neighboring cells. The aim of the present commentary is to concentrate on the biochemical steps in Ca2+ homeostasis that are controlled by NO and to describe what is known thus far concerning the molecular mechanisms of its action. Particular attention will be given to the effects of NO on: (i) inositol 1,4,5-trisphosphate and cyclic ADP ribose generation; (ii) Ca2+ release from both inositol 1,4,5-trisphosphate-sensitive and ryanodine-sensitive Ca2+ stores; and (iii) Ca2+ influx via both store- and second messenger-operated Ca2+ channels. The evidence discussed here documents the complexity of the interactions between the Ca2+ and the NO signalling systems, which represent an extraordinary example of cross-talk operating at multiple sites and which are continuously active in the regulation of cytosolic Ca2+ (and NO) levels.
Clementi
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Department of Pharmacology, Faculty of Pharmacy, CNR-IBAF, University of Reggio Calabria, Catanzaro, Italy. clemene@dibit.hsr.it
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D015640:Ion Channel Gating; D008564:Membrane Potentials / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D002118:Calcium