Signaling second messengers

The second messenger is an effector molecule synthesized when a hormone (the first messenger) binds. It stimulates the cell to respond to the original signal. Second messengers also 17.3 allow the signal to be amplified. 

Excitation of smooth muscle via alpha-1 receptors (eg, in the utems, vascular smooth muscle) is accompanied by an increase in intraceUular-free calcium, possibly by stimulation of phosphoUpase C which accelerates the breakdown of polyphosphoinositides to form the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular calcium, and DAG, by activation of protein kinase C, may also contribute to signal transduction. In addition, it is also thought that alpha-1 adrenergic receptors may be coupled to another second messenger, a pertussis toxin-sensitive G-protein that mediates the translocation of extracellular calcium. 

Depletion of ATP in the cells prevents maintenance of the membrane potential, inhibits the functioning of ion pumps, and attenuates cellular signal transduction (e.g., formation of second messengers such as inositol phos phates or cyclic AMP). A marked ATP depletion ultimately impairs the activ-itv of the cell and leads to ceil death. 

At a cellular level, the activation of mAChRs leads to a wide spectrum of biochemical and electrophysiological responses [1, 5]. The precise pattern of responses that can be observed does not only depend on the nature of the activated G proteins (receptor subtypes) but also on which specific components of different signaling cascades (e.g. effector enzymes or ion channels) are actually expressed in the studied cell type or tissue. The observed effects can be caused by direct interactions of the activated G protein(s) with effector enzymes or ion channels or may be mediated by second messengers (Ca2+, DP3, etc.) generated upon mAChR stimulation. 

The majority of GPCRs couple to three families of G protein alpha subunits which differ in their ability to activate three distinct primary signaling cascades. The stimulatory G-protein Gas, positively regulates the activity of adenylyl cyclase causing an increase of intracellular cAMP levels as second messenger. In... 

The regulation of receptor synthesis is a second component of receptor downregulation. It involves processes that reduce gene transcription, mRNA stability, and receptor half-life time. It should be noted that mechanisms in addition to the regulation of the receptor number may account for tolerance development. Second messenger levels and enzyme activities that participate in the signaling of a given receptor are... 

Inositol trisphosphate Receptor/G-protein cascades. As discussed above, IP3 is one of the products of the hydrolysis of PIP2. To say that it acts as a second messenger means that a rise in its concentration occurs as a result of some meaningful event and that the rise causes some other significant event. In terms of information flow, the signal immediately preceding the rise in IP3 is a rise in the concentration of active PLC. This rise is due to the binding of a subset of G-proteins... 

Phosphorylation by protein kinases of specific seryl, threonyl, or tyrosyl residues—and subsequent dephosphorylation by protein phosphatases—regulates the activity of many human enzymes. The protein kinases and phosphatases that participate in regulatory cascades which respond to hormonal or second messenger signals constimte a bio-organic computer that can process and integrate complex environmental information to produce an appropriate and comprehensive cellular response. 

The inositol is present in ph osphatidylinositol as the stereoisomer, myoinositol (Figure 14—8). Phosphatidylinositol 4,5-hisphosphate is an important constituent of cell membrane phosphohpids upon stimulation by a suitable hormone agonist, it is cleaved into diacylglycerol and inositol trisphosphate, both of which act as internal signals or second messengers. 

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