title: Type-1 and type-2 astrocytes are distinct targets for prostaglandins D2, E2, and F2 alpha.
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. PGF2 alpha, PGD2, and 9 alpha,11 beta-PGF2, a metabolite of PGD2 and a stereoisomer of PGF2 alpha, 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. PGF2 alpha and 9 alpha,11 beta-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 greater than PGE1 greater than or equal to STA2 much greater than iloprost, a stable analogue of PGI2. PGD2 and PGF2 alpha had no effect on cyclic AMP formation. These results demonstrate that type-1 astrocytes preferentially express PGF2 alpha 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.
authors.affiliation: Department of Cell Biology, Osaka Bioscience Institute, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Sugama
authors.forename: N
authors.initials: N
authors.lastname: Inagaki
authors.forename: H
authors.initials: H
authors.lastname: Fukui
authors.forename: H
authors.initials: H
authors.lastname: Giles
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: O
authors.initials: O
authors.lastname: Hayaishi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D015237:Dinoprost / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D015230:Prostaglandin D2 / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D010716:Phosphatidylinositols; D015237:Dinoprost; D000242:Cyclic AMP; D015232:Dinoprostone; D015230:Prostaglandin D2; D002118:Calcium