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It is clear that the eicosanoids are involved in crucial physiological processes in vivo such as blood clotting, inflammation, control of vascular tone, renal function, behaviour, and reproductive system (Shimizu and Wolfe, 1990). However, their role within the CNS are less well understood, and despite the evidence of eicosanoid receptors on glia in culture, there are few indications of either their functions or whether they exist on cells in situ.

Prostanoids, particularly of the E series, can exert potent inhibitory effects on autonomic transmitter release in a range of tissues, and have been reported as having anticonvulsive properties (Hertting and Seregi, 1989). Evidence also points to them having a neuromodulatory role. Thus, prostanoids alone have little effect on, for example, noradrenaline release but modify evoked release from brain slices, probably by restricting Ca^+ fluxes (Chiu and Richardson, 1985). Further, it has been demonstrated that prostaglandin E% (PGE2) potentiates dopamine (D%) receptor- mediated potentiation of AA release in Chinese hamster ovary cells, suggesting that it is acting as a paracrine messenger (Di Marzo and Piomelli, 1992). The excitatory actions of prostanoids on neuronal activity take a number of forms; for example, they have been shown to enhance neurotransmitter release, to elicit neuronal depolarisation and induce hyperalgesia through a lowering of the excitation threshold of peripheral nociceptors (Coleman et al, 1990). Additionally, prostanoids induce upper airways

irritancy and cough, as well as gastric irritancy, nausea and vomiting, and have been implicated in hyperthermia, fever and sleep (Hertting and Seregi, 1989). Whether all these actions are manifestations of the same effect is not clear, but it seems clear that prostanoids can profoundly affect neuronal function in many tissues.

Arachidonic acid and its metabolites have been shown to be released by cerebral tissues as a result of ischaemia (Haun et al, 1993; Kunievsky et al, 1992), and may participate in either damaging or protecting neural tissues, depending on the particular AA metabolite produced. Prostacyclin has been shown to protect rat cortical neurons in culture against hypoxia and glutamate-induced injury (Cazevieille et al, 1993). In addition, Renkawek et al (1986) have reported that prostacyclin exerted a cytoprotective effect on neurons via glial cell activity, however, the mechanism involved is unknown. Moreover, hypothermia has been reported to reduce both cellular injury and the release of [^HJ-labelled AA metabolites during anoxic conditions in vitro, the two events presumably being linked (Haun et al, 1993). In addition, when the human astroglial cell line U C -llM G was treated with adverse conditions, such as ATP depletion, membrane phospholipids were degraded, with the release of AA metabolites (Sun et al, 1993). The severity of cell injury could be blocked by inhibitors of PLA2 and PLC.

There is increasing evidence that AA itself may serve as a signal molecule. For example, Murphy and Welk (1989) have shown that A A stimulates PI breakdown in cortical astrocytes. One interesting possibility is that AA is involved in long-term potentiation (LTP). LTP is a model of synaptic plasticity and information storage, which can be produced in the hippocampus by high frequency stimulation of the perforant pathway, and is generally believed to consist of two phases: induction and maintenance (Piomelli and Greengard, 1990). AA has been shown to potentiate the current through N-methyl-D-aspartate (NMDA) receptors, probably due to an increase in channel open probability (Miller et al, 1992). It is released when glutamate raises the

[Ca^+]i; the induction of LTP is triggered by the postsynaptic entry of Ca^+ through the NMD A receptor channel (Williams et al, 1989). These authors suggest that A A increases synaptic efficacy both in vivo and in vitro, and may act as a retrograde messenger in the late (maintenance) stages of LTP. Further to this, there have been reports of AA release from cortical and hippocampal neurons in culture when challenged with NMDA, and the suggestion is that AA modulates the function of NMDA receptors during synaptic transmission and plasticity of the CNS (Sanfeliu et al,

1990, Tapia-Arancibia etal, 1992).

Given the intimacy of astrocytes with the cerebral vasculature, the effect of eicosanoid release on the cerebral circulation is an area of great potential importance. Eicosanoids have been implicated in cerebral vasospasm, which is the major cause of death after subarachnoid haemorrhage, and to a lesser extent, head trauma (Shimizu and Wolfe, 1990). The impairment of prostanoid metabolism during convulsion and their anticonvulsive effects have been demonstrated (Seregi et al, 1984b). After freezing injury to the brain, several prostanoids are formed in the lesion area, and AA release has been observed in brain adjacent to the injury (Shimizu and Wolfe, 1990).

Although astrocytes have demonstrated their ability to synthesise eicosanoids, little is known about the triggers for synthesis and release. Attempts to examine this question have concentrated on the stimulation of receptors coupled to phosphatidylinositol 4,5,- bisphosphate (PIP2) breakdown and Ca^+ mobilisation. PIP2 breakdown yields DAG and inositol 1,4,5-trisphosphate (IP3). The DAG formed may provide a source of AA following metabolism via DAG lipase, while IPg-induced Ca^+ mobilisation could activate a Ca^+-dependent phospholipase, such as PLA2, and the newly available AA from phospholipid breakdown is then subject to cyclooxygenase /lipoxygenase action (Abdel-Latif, 1986). Stimulation of such receptors in a variety of tissues promotes

eicosanoid release. Despite the fact that astrocytes possess an array of receptors coupled to the PI/Ca^+ second messenger release, activation of the vast majority of them fails to evoke eicosanoid release (Pearce and Murphy, 1988). Stimuli which either increase [Ca^+Ji (Ca^+ ionophores), directly stimulate PLA% (melittin) or activate protein kinase C (phorbol esters), have been shown to elicit eicosanoid release from