Second messengers cyclic nucleotides

For the receptors that bind atrial natriuretic peptides and the peptides guanylin and uroguanylin, the intracellular domain is not a protein kinase but rather a guanylyl cyclase that synthesizes the second messenger cyclic guanosine monophosphate (cyclic GMP), which activates a cyclic GMP-dependent protein kinase (PKG) and can modulate the activities of several cyclic nucleotide phosphodiesterases, among other effectors. 

Calmodulin and cyclic nucleotide-dependent second messenger systems... 

Cyclic nucleotides (cAMP and cGMP) are formed enzymatically from the corresponding triphosphates. As ubiquitous second messengers, they mediate many cellular functions which are initiated by first (extracellular) messengers. Their prime targets in eucaryotic cells are protein kinases ( cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase), ion channels and ensymes. 

The intracellular processes which precede membrane activation appear to differ from those of MOE neurones, in that cyclic nucleotide gating may not occur. The transduction process which induces current flow in snake VN neurones, utilises as a putative second-messenger the modulator compound inositol triphosphate — Ins. (1,4,5) P3 = IP3 (Liu et al, 1999 Taniguichi et al, 2000). The proposed channel component associated with the microvillous membrane is one of the transient receptor potential family (TRPC-2 Heading Fig., pp. 94), the p-splice... 

The most common second messenger activated by protein/peptide hormones and catecholamines is cyclic adenosine monophosphate (cAMP). The pathway by which cAMP is formed and alters cellular function is illustrated in Figure 10.1. The process begins when the hormone binds to its receptor. These receptors are quite large and span the plasma membrane. On the cytoplasmic surface of the membrane, the receptor is associated with a G protein that serves as the transducer molecule. In other words, the G protein acts as an intermediary between the receptor and the second messengers that will alter cellular activity. These proteins are referred to as G proteins because they bind with guanosine nucleotides. In an unstimulated cell, the inactive G protein binds guanosine diphosphate (GDP). When the hormone... 

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. 

G-proteins are easy. The GTP-bound form can interact successively with several molecules of its target before the GTP is hydrolyzed and the G-protein is inactivated. The synthesis of cyclic nucleotide second messengers by the cyclase is also an obvious amplification step. 

G-proteins are so called because they bind a guanosine nucleotide, either GTP or GDP. Their transduction mechanism involves the production of a second messenger such as 3 5 cAMP, 3 5 cyclic GMP (cGMP) or IP3 and diacylglycerol (DAG), derived from AMP, GMP and phosphatidyl inositol-3,5bisphosphate respectively (Figure 4.15). It is the second messenger that initiates the downstream amplification process phase of transduction. 

Inhibition of cyclic nucleotide phosphodiesterases is widely accepted as the predominant mechanism by which theophylline produces bronchodilation. Phosphodiesterases are enzymes that inactivate cAMP and cyclic guanosine monophosphate (GMP), second messengers that mediate bronchial smooth muscle relaxation. 

Cells respond to their environment by taking cues from hormones or other external chemical signals. The interaction of these extracellular chemical signals ( first messengers ) with receptors on the cell surface often leads to the production of second messengers inside the cell, which in turn leads to adaptive changes in the cell interior (Chapter 12). Often, the second messenger is a nucleotide (Fig. 8-42). One of the most common is adenosine 3, 5 -cyclic monophosphate... 

Cyclic AMP, the intracellular second messenger in this system, is short-lived. It is quickly degraded by cyclic nucleotide phosphodiesterase to 5 -AMP (Fig. 12-12, step (7)), which is not active as a second messenger ... 

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. 

Dopamine activates adenylate cyclase and phospholipase C (PLC) via a D, receptor and inhibits through a D2 receptor, thereby regulating the production of intracellular second messengers, cAMP, Ca2+, and 1,2-diacylglycerol. D, and D2 receptors are decreased in the striatum of patients with dementia. There is considerable evidence to suggest that intracellular levels of cAMP have a protective role for dopaminergic neurons. Intracellular concentrations of cyclic nucleotides are regulated by cyclic nucleotide phosphodiesterases and CaMPDE, one of the most intensely studied and best-characterized phosphodiesterases. 

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. 

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