PROSTAGLANDIN PRODUCTION IN CULTURED CEREBRAL MICROVASCULAR SMOOTH-MUSCLE IS SERUM DEPENDENT

To expand the understanding of cerebrovascular eicosanoid metabolism, the ability of smooth muscle isolated from murine cerebral microvessel s to produce prostaglandins (PGs) was studied in vitro. Cultures from SJL and BALB/c mice produced primarily prostaglandin E(2) (PGE(2)) and I-2 (PGI(2)) in response to exogenous arachidonate and calcium ionoph ore as well as the agonists acetylcholine and epinephrine. Subconfluen t smooth muscle cultures demonstrated a two- to threefold increased ca pacity to produce PG compared with confluent cultures. In contrast, se rum deprivation of smooth muscle caused an 80-90% diminution in both P GE(2) and PGI(2) production but had no effect on PG release in cerebro microvascular endothelium. Reintroduction of serum to smooth muscle re stored PG; production within 6 h, and the restoration was inhibited by 1 mu M dexamethasone. Message for both prostaglandin H synthase (PGHS )-1 and -2 was detectable in smooth muscle grown in the presence of se rum, but PGHS-2 message was not present in serum-deprived cultures. Fu rthermore, readdition of serum induced a massive increase in PGHS-2 mR NA with only a small increase in PGHS-1 message. The serum induction o f PGHS-2 was corroborated by immunohistochemistry and Western blotting . Thus cerebromicrovascular smooth muscle may contribute significantly to the formation of PG under circumstances likely to be present durin g central nervous system pathologies. The induction of PGHS, particula rly PGHS-2, may play a key role in this process.