Cyclic nucleotides functional roles

Ingram SL, Williams JT (1996) Modulation of the hyperpolarization-activated current (Ih) by cyclic nucleotides in guinea-pig primary afferent neurons. J Physiol 492 ( Pt 1) 97 106 Ito M (2001) Cerebellar long-term depressionxharacterization, signal transduction, and functional roles. Physiol Rev 81 1143-95... 

However, at this point a role for other second messengers in insect olfaction cannot be excluded. In fact, the observation that distinct cyclic nucleotide-gated ion channels are expressed in insect antennae (Baumann el al., 1994 Krieger el al., 1999a) may be the first evidence for functional implications of a cyclic nucleotide pathway. 

Very recent efforts to further evaluate the functional implications of phosphoinositol signaling in vertebrate chemosensory transduction have led to the discovery that not only the phosphoinositol breakdown pathway catalyzed by phospholipase C, but also membrane phosphoinositols themselves involving phosphoinositide-3-kinase may play a functional role in the transduction process. It was found that 3-phosphoinositides signaling in concert with the canonical phosphoinositide turnover pathway modulate the cyclic nucleotide signaling cascade downstream of the receptor. The data suggest that 3-phosphoinositide, the primary product of PI3K activity, attenuates the cyclic nucleotide-dependent excitation of olfactory neurons (Spehr et al., 2002). 

Strom, T, B., Lundin, A. P. and Carpenter, C. B. (1977). The role of cyclic nucleotides in lymphocyte activation and function Pntg. Clin. Immunol. 3, 115-153,... 

The central role of cyclic nucleotides in regulating a wide range of important biological functions requires examination of the mechanisms of their enzymic synthesis and breakdown. Above all, their biological importance demands a response to the question What design feature of cyclic nucleotides makes these molecules ideal as intracellular messengers In the light of the subject of this review, we must add the rider Is there a role for nucleophilic substitution at phosphorus in protein kinase activation ... 

The amount of nucleosides in cells is negligible also deoxyribonucleotides occur at insignificant levels in tissues. Ribonucleotides are important cellular components and occur as 5 -monophosphates, di-, tri-, and cyclic 3, 5 -phos-phates. Nucleoside phosphates function as energy carriers and serve as precursors for the synthesis of nucleic acids. Cyclic nucleotides (i.e., cyclic 3, 5 -AMP and cyclic-3, 5 -GMP) also play a role in metabolic regulation. 

Although cyclic AMP and cyclic GMP appear to mediate antagonistic events in many systems support for the simplistic view that they always have antagonistic functions is dwindling. Newer studies appear to stress the independent role played by each cyclic nucleotide in the mediation of specific cellular responses. Thus, the demonstration of the existence and reciprocal responsiveness of cyclic GMP in a particular system is no longer sufficient to assign to it merely a role as an antagonist of cyclic AMP in that system. 

Like all regulatory GTPases, the heterotrimeric G proteins run through a cyclical transition between an inactive, GDP-bound form and an active, GTP-bound form. Thereby, the activated G protein-coupled receptor functions as a nucleotide exchange factor, GEF. Figure 5.18 sketches the different functional states and the role of the individual subunits. 

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