Role of Nitric Oxide and Its Intracellular Signalling Pathways in the Control of Ca2 Homeostasis (original) (raw)

1998, Biochemical Pharmacology

Ca 2ϩ , a primary regulator of physiological functions in all cells, is involved in a variety of intracellular signalling pathways; control of Ca 2ϩ homeostasis is, therefore, a fundamental cell activity. To this end, cells have developed a variety of mechanisms to ensure the buffering of Ca 2ϩ , 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 Ca 2ϩ 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 Ca 2ϩ 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) Ca 2ϩ release from both inositol 1,4,5-trisphosphate-sensitive and ryanodine-sensitive Ca 2ϩ stores; and (iii) Ca 2ϩ influx via both store-and second messenger-operated Ca 2ϩ channels. The evidence discussed here documents the complexity of the interactions between the Ca 2ϩ 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 Ca 2ϩ (and NO) levels. BIOCHEM PHARMACOL 55;6:713-718, 1998. † Abbreviations: NO, nitric oxide; [Ca 2ϩ ] i , intracellular Ca 2ϩ concentration; IP 3 and IP 3 R, inositol 1,4,5-trisphosphate and its receptor; RyR, ryanodine receptor; PLC, phospholipase C; G kinase, cGMP-dependent protein kinase I; cADP ribose, cyclic ADP ribose; SOCC and SMOC, store-operated and second messenger-operated Ca 2ϩ channels; and cGMP, cyclic GMP.