Nucleotides, cyclic, and calcium

Second messengers relay the primary signal. The distinction between second messengers and normal transducers is that second messengers are small molecules. Extracellular signals of various kinds can activate intracellular pathways that cause an increase in the concentration of a small molecule messenger. All of these pathways involve G-protein coupled receptors. There are two second messengers that you need to know about cyclic nucleotides and calcium. 

Relationship of Cyclic Nucleotides and Calcium in Platelet Function... 

Berridge, M.J. (1975) The interaction of cyclic nucleotides and calcium in the control of cellular activity. Adv. Cycl. Nucleotide Res. 6 1-98. 

The second messenger molecules Ca2+ and cyclic AMP (cAMP) provide major routes for controlling cellular functions. In many instances, calcium (Ca2+) achieves its intracellular effects by binding to the receptor protein calmodulin. Calmodulin has the ability to associate with and modulate different proteins in a Ca2+-dependent and reversible manner. Calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE, EC 3.1.4.17) is one of the key enzymes involved in the complex interactions that occur between the cyclic-nucleotide and Ca2+ second messenger systems (see Figure 13.2). CaMPDE exists in different isozymic forms, which exhibit distinct molecular and catalytic properties. The differential expression and regulation of individual phosphodiesterase (PDE) isoenzymes in different tissues relates to their function in the body. 

Kaneko S, Akaike A, Satoh M (1998) Differential regulation of N- and Q-type Ca2+ channels by cyclic nucleotides and G-proteins. Life Sci 62 1543-7 Kang MG, Campbell KP (2003) Gamma subunit of voltage-activated calcium channels. J Biol Chem 278 21315-8... 

In brain, a large number of particulate soluble proteins are phosphory-lated in the presence of Mg " -ATP and Ca +—calmodulin. These phosphorylations can be blocked by phenothiazines and do not occur in the presence of cAMP or cGMP. Furthermore, they are unaltered by the Walsh inhibitor, which is specific for the cAMP catalytic subunit. Hence, investigators have concluded that there is present in both particulate and soluble fractions of brain a Ca " -calmodulin-dependent protein kinase that is insensitive to cyclic nucleotides and that contains its own set of protein substrates. A few reports have appeared in the literature claiming purification of a calcium-calmodulin-dependent kinase from mammalian brain. The en-... 

Mazzotta, J. B. Nguyen, D. Ebens, A. J. Winslow, J. Recombinant cell and method for identifying insect cyclic nucleotide-gated calcium channel agonists for use as insecti-cides. Ger. Offen. DE 102004062273, 2006 Chem. Abstr. 2006, 145, 120011. 

There are several mechanisms involved in the vasodilator effect of flavonoids. The main mechanism seems to be related to the inhibition of protein kinase C or some of the processes activated by this protein. The inhibition of other protein kinases and cyclic nucleotide phosphodiesterase activity and blockage of calcium entry can also contribute to this effect to a greater or lesser extent (Alvarez Castro and Orallo, 2003 Herrera and others 1996). Certain flavonoids, like the flavonol myricetin, have a two-phase action on blood vessels vasoconstrictor in lowest active concentrations and vasodilator in higher concentrations (Alvarez Castro and Orallo, 2003). 

Trudeau, M. C. and Zagotta, W. N. Calcium/calmodulin modulation of olfactory and rod cyclic nucleotide-gated ion channels. /. Biol. Chem. 278 18705-18708, 2003. 

Katz, A. M., Tada, M., and Kirchberger, M. A. (1975) Control of calcium transport in the myocardium by the cyclic AMP-protein kinase system. In Advances in Cyclic Nucleotide Research, Vol. 5, edited by G. 1. Drummond, P. Greengard, and G. A. Robinson, pp. 453-472. Raven Press, New York. 

While ionophore-stimulated 5-LO product release from neutrophils is often used as an indication of 5-LO inhibition, one must interpret these results cautiously. For example, halothane, an inhalation anaesthetic which may cause membrane perturbation [26], and colchicine, a microtubule disrupter [27], both were active, but presumably not because of 5-LO inhibition. A23187 is assumed to stimulate 5-LO by raising the intracellular calcium level, but this agent causes many other effects which may or may not be related to 5-LO activation, including changes in membrane potential, protein phosphorylation, phospholipid turnover, cyclic nucleotide levels, and DNA and protein synthesis [28]. Also, the effects of some putative 5-LO inhibitors on product release from neutrophils has been shown to vary with the stimulant used [29]. 

Fonagy A., Matsumoto S., Uchhiumi K. and Mitsui T. (1992a) Role of calcium ion and cyclic nucleotides in pheromone production in Bombyx mori. J. Pest. Sci. 17, 115— 121. 

The regulatory role of calcium ions in intermediary metabolism is well documented. Calcium has been shown to be involved in activation or inhibition of specific enzyme systems [105], For example, it activates cyclic nucleotide phosphodiesterase, phosphofructokinase, fructose 1 6 biphosphatase, glycerol phosphate dehydrogenase, pyruvate dehydrogenase phosphatase and pyruvate dehydrogenase kinase. Calcium ions inhibit pyruvate kinase, pyruvate carboxylase, Na+/K+-AT-Pase and adenylate cyclase. 

---