Arachidonic acid signaling

Studies on A -methyl,4-phenyl-l,2,3,6 tetrahydropyridine (MPTP)-induced model of PD indicate that activities of PLA2, COX-2, and rate of lipid peroxidation are increased (Table 8.3), and PLA2, COX inhibitors, and some antioxidants protect neural cells from MPTP-mediated neurodegeneration (Yoshinaga et al., 2000 Teismann et al., 2003 Farooqui et al., 2006). Similarly, arachidonic acid signaling is upregulated in the caudate-putamen and frontal cortex of unilaterally... 

Nitric Oxide and Arachidonic Acid Signaling are Linked through... 

Nitric Oxide and Arachidonic Acid Signaling are Linked through Nitro-Fatty Acids Modulation of Prostaglandin Endoperoxide H Synthase... 

Barlow RS, El-Mowafy AM, White RE. H2O2 opens BK(Ca) channels via the PLA2-arachidonic acid signaling cascade in coronary artery smooth muscle. Am J Physiol 2000 279 H475-H483. 

Leukotrienes and Prostanoids. Arachidonic acid (AA) (213) and its metabohtes are iavolved ia cellular regulatory processes ia all three principal chemical signaling systems endocrine (see Hormones), immune, and neuronal (62). FoUowiag receptor activation or iacreased iatraceUular... 

Functionally, the Dl-like receptors (Dl, D5) are coupled to the G protein Gas and thus can stimulate adenylyl cyclase. The D2-like receptors (D2, D3, and D4) couple to pertussis toxin sensitive G proteins (Gai/0), and consequently inhibit adenylyl cyclase activity. While the Dl-like receptors almost exclusively signal through Gas-mediated activation of adenylyl cyclase, the D2-like receptors have been reported to modulate the activity of a plethora of signaling molecules and pathways. Many of these actions are mediated through the G(3y subunit. Some of these molecules and pathways include the calcium channels, potassium channels, sodium-hydrogen exchanger, arachidonic acid release, and mitogen-activated protein kinase pathways. 

TBT and TFT are membrane-active molecules, and their mechanism of action appears to be strongly dependent on organotin(IV) lipophilicity. They function as ionophores and produce hemolysis, release Ca(II) from sarcoplasmic reticulum, alter phosphatodylseiine-induced histamine release, alter mitochondrial membrane permeability and perturb membrane enzymes. Organotin(IV) compounds have been shown to affect cell signaling they activate protein kinase and increase free arachidonic acid through the activation of phospholipase... 

Second-derivative spectrophotometry has been used to monitor the time-dependent production of cis,tmns-(Xmax 242 nm) and trans, tram- (Xmax 232 nm) diene conjugates of microsomal PUFAs following the exposure of rats to carbon tetrachloride (CCU) (Corongui et al., 1986). These signals have been postulated to be derived from mixtures of peroxidized substrates. Previous studies using chemical model systems have established that autoxidation of linolenic or arachidonic acid results in the production of cis, trans- and tmns, trawr-conjugated diene... 

Less explored is the role and metabolic fate of 2-AG. It is possible that in many tissues, 2-AG is only an intermediate of a signaling pathway that generates 1,2-diacylglycerol and arachidonic acid, two well-known signaling molecules. In the brain however, 2-AG may have regulatory roles, since it escapes immediate metabolism and accumulates in response to stimuli-generated Ca2+ surges (Stella, 1997). These differences may arise... 

The family of heterotrimeric G proteins is involved in transmembrane signaling in the nervous system, with certain exceptions. The exceptions are instances of synaptic transmission mediated via receptors that contain intrinsic enzymatic activity, such as tyrosine kinase or guanylyl cyclase, or via receptors that form ion channels (see Ch. 10). Heterotrimeric G proteins were first identified, named and characterized by Alfred Gilman, Martin Rodbell and others close to 20 years ago. They consist of three distinct subunits, a, (3 and y. These proteins couple the activation of diverse types of plasmalemma receptor to a variety of intracellular processes. In fact, most types of neurotransmitter and peptide hormone receptor, as well as many cytokine and chemokine receptors, fall into a superfamily of structurally related molecules, termed G-protein-coupled receptors. These receptors are named for the role of G proteins in mediating the varied biological effects of the receptors (see Ch. 10). Consequently, numerous effector proteins are influenced by these heterotrimeric G proteins ion channels adenylyl cyclase phosphodiesterase (PDE) phosphoinositide-specific phospholipase C (PI-PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and phospholipase A2 (PLA2), which catalyzes the hydrolysis of membrane phospholipids to yield arachidonic acid. In addition, these G proteins have been implicated in... 

Although arachidonic acid is widely implicated in signaling in brain, there are several gaps in our understanding of the release of this fatty acid from membrane reservoirs. 

Horrocks, L. A. and Farooqui, A. A. NMDA receptor-stimulated release of arachidonic acid mechanisms for the Bazan effect. In Municio, A. M. and Miras-Portugal, M. T. (eds), Cell Signal Transduction, Second Messengers, and Protein Phosphorylation in Health and Disease. New York Plenum Press, 1994, pp. 113-128. 

Fig. 10. Photoaffinity probes for studying G-protein interactions PLC/IP3/Ca2+ signaling pathways, and the arachidonic acid cascade ...

Berridge MJ 1997 Elementary and global aspects of calcium signalling. J Physiol 499 291—306 Broad LM, Cannon TR, Taylor CW 1999 A non-capacitative pathway activated by arachidonic acid is the major Ca2+ entry mechanism in rat A7r5 smooth muscle cells stimulated with low concentrations of vasopressin. J Physiol 517 121-134 Byron KL, Taylor CW 1995 Vasopressin stimulation of Ca2+ mobilization, two bivalent cation entry pathways and Ca2+ efflux in A7r5 rat smooth muscle cells. J Physiol 485 455—468... 

Figure 1 The MAPK pathway and its connections to other signals A negative feedback loop connects the phosphorylated endpoint of the pathway ERK (Extracellular-signal Regulated Kinase) to the transcriptionally-driven synthesis of the phosphatase, MKP MAP kinase phosphatase. MKP then de-phosphorylates ERK to shut down the signaling cascade. The positive feedback loop again starts with the terminal kinase ERK which activates cPLA2 (cytosolic phospholipase A2). This leads to the synthesis of arachidonic acid, which, in turn activates protein kinase C (PKC). PKC is a positive regulator of RAS (Please see Color Plate Section in the back of this book).

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