Astrocytes as eicosanoid‐producing cells

Abstract

A variety of prostaglandins and leukotrienes, together with thromboxane and prostacyclin metabolites, can be detected in central nervous tissues and in cerebrospinal fluid. Defined cultures of astrocytes have revealed these cells to be a major source of eicosanoids. In common with other eicosanoid-producing cells, agents such as calcium ionophores and phorbol esters are potent stimuli for promoting release. While in other tissues agonists for receptors linked to calcium mobilisation prompt eicosanoid release, this does not seem to be the case in astrocytes, though a range of such receptors are present. The notable exceptions to this observation are adenosine triphosphate and adenosine diphosphate, presumably acting through P2 purinergic receptors. Many cell types in the CNS are targets for eicosanoids, possessing receptors linked to adenylate cyclase or phospholipase C. An appreciation of the functional significance of activation of these receptors is just now beginning. Eicosanoids have effects in the CNS that involve not only the vascular supply but also synaptic modulation and immune regulation.

Transforming Growth Factor β1 Regulates the Expression of Cyclooxygenase in Cultured Cortical Astrocytes and Neurons

“…Nevertheless, despite the similar amount of COX in astrocytes and neurons, prostaglandin production is higher in astrocytes than in neurons. Thus, our data are consistent with published in vitro studies (e.g., Seregi et al, 1984;Murphy et al, 1988) showing that astrocytes are an important source of prostanoids. The reader should note, however, that one study shows COX2 expression mainly in cultured neurons, whereas glial expression is very low (Kawasaki et al, 1993).…”

“…PGE2 was measured, because this specific prostanoid is produced abundantly by rat astrocytes (Murphy et al, 1988). The amount of cell-generated PGE2 ideally should be normalized with the concentration of PGE2 in a medium containing either 1.0% or 10% FCS.…”

Augmented Vasoconstriction and Thromboxane Formation by 15-F 2t -Isoprostane (8-Iso-Prostaglandin F 2α ) in Immature Pig Periventricular Brain Microvessels

“…44 Of the vascular and perivascular cells studied, thromboxane generation in response to 15-F 2t -IsoP arose largely from endothelial and astroglial cells ( Figure 4); 15-F 2t -IsoP was ineffective on smooth muscle cells. Because astrocytes, which release vasoactive substances, 45,46 are the most abundant cell type in brain parenchyma, it is reasonable to suggest that astrocytes are the main source of thromboxane formation and contribute most to 15-F 2t -IsoP-mediated constriction; this inference is supported by inhibition of constriction by -conotoxin (Figure 6), which inhibits thromboxane generation only in astrocytes (Figure 4). Thus, 15-F 2t -IsoPinduced constriction is mediated by thromboxane released mainly from astrocytes as well as from vascular endothelial cells, but not from smooth muscle.…”

Involvement of transforming growth factor alpha in the release of luteinizing hormone-releasing hormone from the developing female hypothalamus.

“…However, the 2-h lag time needed for the TGF-a/EGF effect to become evident argues in favor of an indirect effect that may be mediated by cellular elements of the ME associated with LHRH nerve terminals. That these cells may be glia is suggested by the observations that most EGF receptors are found in glial cells (10,34) and that astrocytes produce PGE2 and other eicosanoids in response to neurotransmitter or neuropeptide stimulation (35,36). Recently, a subpopulation of astrocytes has been shown to synthesize TGF-a, as evidenced by their immunoreactivity to TGF-a precursor antibodies (4).…”