Receptors that Stimulate Arachidonate Mobilization

Animal cells have evolved two sorts of mechanisms to increase arachidonate mobilization in response to external stimuli shortterm mechanisms, which evolve over a time-scale of seconds to minutes and do not depend on the synthesis of new proteins, and long-term mechanisms, which evolve over several hours and do depend on protein synthesis. 

In CHO cells, the stimulation of constitutive P2-type purinergic receptors by extracellular ATP produces two prominent responses activation of phosphoinositide-specific PLC, which leads to inositoltrisphosphate-induced elevations of intracellular calcium levels, and formation of free arachidonate from membrane phospholipids. Evidence from both pharmacological and genetic experiments. 

Let us turn now to our second example of short-term arachidonate mobilization the receptor-dependent activation of group II PLA2 in P388Di cells. Stimulation of these cells with li-popolysaccharide or PAF mobilizes arachidonate in two phases a transient phase (maximal at -1.5 minutes and rapidly declining 

How may activation take place under those conditions We don t know yet, but a possible scenario (composed from results 

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We have seen that a series of first messenger signaling molecules produce arachidonate mobilization by activating membrane receptors. Too many such effects have been described over the past 20 years to allow me to compile a review of this subject area that is both exhaustive and useful. I will rather illustrate with some examples what I consider to be the three major modalities of receptor-mediated control of arachidonate mobilization stimulation, inhibition and facilitation. Where possible, I will also indicate the specific transmembrane signaling pathway and enzyme route affected. 

In many cell types, D2 receptor stimulation has an effect on enzymes metabolizing membrane lipids. We have mentioned above that in mesenchyme-derived cells and in striatal neurons, D2 agonists stimulate the activity of PLCp by mobilizing Gpy complex, and produce an inositol triphosphate-dependent Ca2+ release from intracellular stores (Ghahremani et al., 1999). In CHO cells stably transfected with D2 receptors, D2 agonists potently enhance the release of arachidonic acid when intracellular Ca2+ levels are already enhanced. This effect was observed following stimulation of various Gi/o-coupled... 

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