Phosphoinositide Hydrolysis Indicates Functional Receptors in Astrocytes and in Neoplastic Cells from the Human CNS

Abstract

Astrocytes, the majority cell type in the CNS, have the potential to play a dynamic role in intercellular communication. Situated adjacent to neurons and to cells of the microvasculature, these glial cells display a variety of surface receptors (Murphy and Pearce, 1987). Astrocytes synthesize and release peptide mediators, such as met-enkephalin, somatostatin, endothelin-1 and -3 (Shinoda et al., 1989; MacCumber et al., 1990; Ehrenreich et al., 1991), and eicosanoids including prostaglandins E2, F2ûr, D2, thromboxane A2, and the leukotrienes LTB4 and LTC4 (Murphy et al., 1988). Regulation of the synthesis and release of many of these agents from astrocytes is not completely understood. We have focussed on the mechanism by which prostanoid production in astrocytes is regulated by purinergic (P_2y) receptor agonists. Most recently, we have demonstrated the evoked release of an astrocyte-derived (vaso)relaxing factor (ADRF) which is not a prostanoid but a nitrosyl compound with properties similar to nitric oxide. Thus, activation of specific receptors induces the synthesis and release of products from astrocytes with the potential to directly affect not only neuronal, but also vascular cell function.