Requirement of Calcium Ion for NO Formation

Early studies established the basic requirement of extracellular calcium ion for hormone-dependent alterations in cGMP contents (Schultz et al., 1973). Following this report, while many investigators attributed calcium participation in the hormone action through some sort of calmodulininvolving manner (Mittal and Murad, 1982), the exact mode or mechanism 

Enough experimental evidence has accumulated over the past few years to make a compelling case for the involvement of calcium ion in the generation of NO in various tissues and organs. The first demonstration of a calcium requirement for in vitro expression of NOS catalytic activity came from the studies by Knowles et al. (1989), using both the L-citrulline and cGMP assays. Subsequently, these results have been confirmed by many laboratories (Bredt and Snyder, 1990 Forstermann et al., 1991a Mittal, 

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