Evidence that prostaglandin E2 can block calcium-activated 86Rb efflux from rat brain synaptosomes via a protein kinase C-dependent mechanism.

The effects of prostaglandin E2 (PGE2) on 86Rb efflux from rat brain synaptosomes were studied to explore its role in nerve ending potassium (K+) channel modulation. A selective dose-dependent inhibition of the calcium-activated charybdotoxin-sensitive component of efflux was found upon application of PGE2. 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 microM) 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 PGE2-induced inhibition, whereas HA1004 (10 microM) and Rp-3',5'-cyclic phosphorothioate (100 nM), which are 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 Ca(2+)-dependent component of 86Rb efflux but also had no effect on the basal and voltage-dependent components. These data suggest that PGE2 can inhibit rat brain nerve ending calcium-activated 86Rb efflux, and this inhibition may involve PKC activation.