Stimuli, extracellular

Grb-2 facilitates the transduction of an extracellular stimulus to an intracellular signaling pathway, (b) The adaptor protein PSD-95 associates through one of its three PDZ domains with the N-methyl-D-aspartic acid (NMDA) receptor. Another PDZ domain associates with a PDZ domain from neuronal nitric oxide synthase (nNOS). Through its interaction with PSD-95, nNOS is localized to the NMDA receptor. Stimulation by glutamate induces an influx of calcium, which activates nNOS, resulting in the production of nitric oxide. 

IP3 Receptors. Figure 1 Interplay between Ca2+ channels. Ca2+ signals are initiated when an extracellular stimulus (red) directly opens a Ca2+ channel in the plasma membrane or indirectly, via a signalling pathway (green), opens an intracellular Ca2+ channel. Ca2+ signals may then be propagated across the cell by Ca2+-induced Ca2+ release mediated by IP3R or RyR. 

Cells respond to some extracellular factors such as leukotriene B (Ford-Hutchin-son et al., 1980) by increasing the locomotion rate in an undirected manner as opposed to chemotaxis. This mechanism, known as chemokinesis, is likely on purely statistical grounds to result in cells accumulating at the site of origin of this stimulus (Wilkinson, 1987). The differentiation of factors that are chemotactic from chemokinetic responses can be difficult, but this has been greatly facilitated using the Boyden chamber (Lackie, 1986). 

In conclusion, the role of chemokines and their receptors continue to be investigated in asthmatic diseases. The role of specific chemokine receptor/ ligand systems will depend upon the nature of the inciting stimulus (i.e., non-infectious vs. infectious), as well as the intracellular (viral) versus extracellular (fungal) nature of microbes. Given the broad nature of the classification of asthmatic disease, a number of chemokine receptors as potential targets continue to be relevant. 

Immediately after synthesis, endocannabinoids are released in the extracellular space, where they then act on the same or neighboring cells as autocrine or paracrine mediators (Di Marzo, 1999). Experimental evidence thus far indicates that anandamide and 2-AG, unlike other classical neurotransmitters, are not stored in vesicles. First, anandamide basal concentrations are extremely low (5-10 pmol/g), 100 to 10,000 times lower than those of classical neurotransmitters (Cadas, 1997). Second, stimulus-dependent anandamide release is linked with de novo NAPE and... 

The osmoreceptors of the hypothalamus monitor the osmolarity of extracellular fluid. These receptors are stimulated primarily by an increase in plasma osmolarity they then provide excitatory inputs to the thirst center and the ADH-secreting cells in the hypothalamus. The stimulation of the thirst center leads to increased fluid intake. The stimulation of the ADH-secreting cells leads to release of ADH from the neurohypophysis and, ultimately, an increase in reabsorption of water from the kidneys and a decrease in urine output. These effects increase the water content of the body and dilute the plasma back toward normal. Plasma osmolarity is the major stimulus for thirst and ADH secretion two additional stimuli include ... 

A more moderate stimulus for thirst and ADH secretion is a decrease in extracellular fluid, or plasma volume. This stimulus involves low-pressure receptors in the atria of the heart as well as baroreceptors in the large arteries. A decrease in plasma volume leads to a decrease in atrial filling, which is detected by low-pressure receptors, and a decrease in MAP, which the baroreceptors detect. Each of these receptors then provides excitatory inputs to the thirst center and to the ADH-secreting cells. 

Shaywitz, A.J., Greenberg, M.E. CREB a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu. Rev. Biochem. 68 821, 1999. 

As outlined in previous sections, escape of polyplexes from endosomes to the cytosol can be a major bottleneck in delivery. Membrane-active polymer domains or other conjugated molecules can help to overcome this barrier (see Sect. 2.3), but they may trigger cytotoxicity when acting extracellularly or at the cell surface. Therefore membrane-crossing agents either have to be inherently specific for endo-somal compartments (for example by pH-specificity), or they have to be modified to be activated in endosomes. For example, the reducing stimulus of intracellular vesicles has been used to activate formulations containing less active disulfide precursors of LLO [163] or Mel [170]. 

Figure 4.8. Hypothesis for the local generation of mast-cell-stimulating peptides by the action of neutrophil-derived enzymes on albumin. Initial stimulation of the mast cell by any of a variety of agents causes the release of preformed histamine (H) neutrophil and eosinophil chemotactic factors (NCF, ECF) and enzymes and the de novo synthesis of prostaglandins (PG) and leukotrienes (LT). These agents increase vascular permeability and vessel diameter. As a result, albumin and later neutrophils (PMN) enter the tissue space where the latter undergo phagocytosis and the secretion of proteolytic enzymes to the extracellular space where they act on albumin to generate NRP (neurotensin-related peptide) and HRP (histamine-releasing peptide). These newly formed peptides then act as a second stimulus to the mast cell. In addition NRP and HRP may affect other immunocompetent celt such as monocytes, macrophages or eosinophils.

Cardiac glycosides (CG) bind to the extracellular side of Na+/lC-ATPases of cardiomyocytes and inhibit enzyme activity. The Na+/lC-ATPases operate to pump out Na+ leaked into the cell and to retrieve 1C leaked from the cell. In this manner, they maintain the transmembrane gradients for 1C and Na+, the negative resting membrane potential, and the normal electrical excitability of the cell membrane. When part of the enzyme is occupied and inhibited by CG, the unoccupied remainder can increase its level of activity and maintain Na and 1C transport The effective stimulus is a small elevation of intracellular Na concentration (normally approx. 7 mM). 

Fig. 7.11. Kinetics of formation of Ins(l,4,5)P3 and diacylglycerol. The figure shows a model for the different dynamics of formation of Ins(l,4,5)P3 and of diacylglycerol (DAG), observed as a consequence of hormonal stimulation in an ideahzed ceU. An extracellular stimulus causes activation of the Ptdins specific phospholipase C (PL-CP or PL-Cy) on a sec timescale, and thus formation of Ins(l,4,5)P3 and DAG, and release of (not shown). The renewed increase in concentration of DAG is caused by the activation of phosphatidyl choline specific phospholipases of type C and phospholipase of type D. According to Liscovitch, (1992).

Neural cells from Aplysia Extracellular response on electrical stimulus [97]... 

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