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.
Ren
J
J
Department of Physiology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Benishin
C G
CG
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018999:Charybdotoxin; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D016548:Prosencephalon / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium / Q000378:metabolism*; D012604:Scorpion Venoms / Q000494:pharmacology; D019311:Staurosporine; D013449:Sulfonamides; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology
D000470:Alkaloids; D002121:Calcium Channel Blockers; D007546:Isoquinolines; D010879:Piperazines; D012604:Scorpion Venoms; D013449:Sulfonamides; D013873:Thionucleotides; D018999:Charybdotoxin; C016957:adenosine-3',5'-cyclic phosphorothioate; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D000242:Cyclic AMP; D011493:Protein Kinase C; D019311:Staurosporine; D015232:Dinoprostone; D012413:Rubidium; D002118:Calcium