Type‐1 and type‐2 astrocytes are distinct targets for prostaglandins D2, E2, and F2α

Abstract

Accumulating evidence has revealed that astrocytes are potential targets for various neurotransmitters. Here we investigated the effects of prostaglandins (PGs) on signal transduction in purified primary cultures of rat type-1 and type-2 astrocytes. PGF_2α, PGD₂, and 9α, 11β-PGF₂, a metabolite of PGD₂ and a stereoisomer of PGF_2α, evoked a rapid rise in the intracellular Ca² concentration ([Ca²⁺]_i) in type-1, but not in type-2, astrocytes. STA₂, a stable analogue of thromboxane A₂, was less effective, and PGE₂ showed little effect. The PG-induced rise in [Ca²⁺]_i was not blocked by an antagonist of either PGD₂ receptor or thromboxane A₂ receptor. PGF_2α and 9α, 11β-PGF₂ stimulated rapid formation of inositol trisphosphate followed by inositol bisphosphate and inositol monophosphate. On the other hand, PGE₂ increased the intracellular level of cyclic AMP in type-2 astrocytes, rather than in type-1 astrocytes. The potency of PGs for cyclic AMP formation was in the following order: PGE₂ > PGE₁ ≥ STA₂ > iloprost, a stable analogue of PGI₂. PGD₂ and PGF_2α had no effect on cyclic AMP formation. These results demonstrate that type-1 astrocytes preferentially express PGF_2α receptors, the activation of which leads to phosphoinositide metabolism and [Ca²⁺]_i elevation, whereas type-2 astrocytes possess PGE receptors that are linked to cyclic AMP formation.