EVIDENCE THAT PROSTAGLANDIN E(2) CAN BLOCK CALCIUM-ACTIVATED RB-86 EFFLUX FROM RAT-BRAIN SYNAPTOSOMES VIA A PROTEIN-KINASE C-DEPENDENT MECHANISM

The effects of prostaglandin E(2) (PGE(2)) on Rb-86 efflux from rat br ain synaptosomes were studied to explore its role in nerve ending pota ssium (K+) channel modulation. A selective dose-dependent inhibition o f the calcium-activated charybdotoxin-sensitive component of efflux wa s found upon application of PGE(2). No significant effect was seen on basal and voltage-dependent components over the concentration range of 10(-8) to 10(-5) M. The protein kinase C (PKC) inhibitors H-7 (10 mu M) and staurosporine (100 nM), as well as prolonged preincubation (90 min) with 4 beta-phorbol 12,13-dibutyrate, which has been reported to down-regulate PKC, abolished the PGE(2)-induced inhibition, whereas HA 1004 (10 mu M) and Rp-3',5'-cyclic phosphorothioate (100 nM), which ar e relatively more selective for protein kinase A than PKC, did not. 4 beta-Phorbol 12,13-dibutyrate (100 nM), an activator of PKC, produced a similar inhibition of the Ca2+-dependent component of Rb-86 efflux b ut also had no effect on the basal and voltage-dependent components. T hese data suggest that PGE(2) can inhibit rat brain nerve ending calci um-activated Rb-86 efflux, and this inhibition may involve PKC activat ion.