Cyclic nucleotides signal transduction

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). 

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... 

Ache and coworkers demonstrated that both cyclic nucleotides and inositol phosphates mediate the transduction of environmental chemical signals by the olfactory neurons of P. argus.62 65 Both biochemical and molecular biological techniques have shown that the receptor cells contain various G-protein subunits that would be necessary for signal detection by G-protein-associated chemoreceptors.48 49 66-69 In combination with electrophysiological studies,... 

The existence of a variety in response kinetics and excitatory and inhibitory responses in the same ORN are not easily explained in terms of a single signal transduction cascade. They hint at the possibility of multiple transduction pathways, as has been demonstrated in lobster ORNs (Ache and Zhainazarov, 1995). This could lead to simple forms of stimulus integration at the level of the ORN (Derby, 2000). Do multiple pathways function in complete isolation or is there crosstalk The presence of a variety of reversal potentials in patch clamp studies of Drosophila antennal ORNs suggests that odorants do not all elicit the same transduction mechanism (Dubin and Harris, 1997). What is the evidence in Drosophila for the presence of transduction element of the main pathways, the cyclic nucleotide pathway and the IP3/DAG pathway Is there coexpression in single neurons ... 

With modest increase in intracellular ROS levels, activation of NF-kB takes place, which protects the cell against oxidative stress [45], Direct root of ROS participation in signal transduction from cell membrane to intracellular metabolic reactions were recently described. Among them - activation of potential-dependent K-channels and variation of membrane potential, inhibition of cellular protein phosphatases and restriction of activity of MAP-kinase [49]. Such view on intracellular role of ROS consider them as second messengers, which together with cyclic nucleotides, calcium ions, and other biologically active compounds provides adequate cell response to the outer signals. 

ASM is rich in receptors for many of the inflammatory mediators. It relies heavily upon pharmacomechanical coupling mechanisms for the transduction of such extracellular signals. In spite of the wide range of extracellular mediators for which the ASM cell expresses receptors, it appears that the diversity of the intracellular signalling mechanisms is more restricted, involving the release of sequestered Ca, turnover of membrane phospholipids such as the phosphoinositides, changes in cytosolic cyclic nucleotide levels, and aaivation of protein kinase enzymes. 

Michel WC (1999) Cyclic nucleotide-gated channel activation is not required for activity-dependent labeling of zebrafish olfactory receptor neurons by amino adds. Biol Signals Recept 8 338-347 Michel WC, Derbidge DS (1997) Evidence of distinct amino acid and bile salt receptors in the olfactory system of the zebrafish, Danio rerio. Brain Res 764 179-187 Michel WC, Sanderson MJ, Olson JK, Lipschitz DL (2003) Evidence of a novel transduction pathway mediating detection of polyamines by the zebrafish olfactory system. J Exp Biiol 206 1697-1706... 

CNG channels (cyclic nucleotide-gated ion channels) are activated by the binding of cyclic GMP. They mediate sensory signal transduction in photoreceptors and olfactory cells. Six mammahan CNG channel genes are known and some human visual disorders are caused by mutations in retinal rod or cone CNG genes. ... 

Tlie second messengers that we have seen recur in many additional signal transduction pathways. For exampile, in a consideration of the sensory systems in Chapter 32, we will see how Ca -based signaling and cyclic nucleotide-based signaling play key roles in vision and olfaction. 

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