Protein kinase C and presynaptic modulation of acetylcholine release in rabbit hippocampus.
1. The involvement of protein kinase C in the presynaptic modulation of stimulated acetylcholine release was investigated in rabbit hippocampus. 2. Slices of the rabbit hippocampus, labelled with [3H]-acetylcholine, were superfused with medium and stimulated electrically during superfusion. 3. The protein kinase C activating phorbol ester 4 beta-phorbol 12,13-dibutyrate (4 beta-PDB) enhanced the electrically evoked tritium overflow in a concentration-dependent manner. Its biologically inactive 4 alpha-isomer was without any effect on transmitter release. 4. The protein kinase C inhibitor polymyxin B decreased the stimulation-evoked tritium overflow and counteracted the enhancement of release caused by 4 beta-PDB. 5. The stimulation-evoked tritium overflow was facilitated when the muscarine receptor antagonist atropine was present. The effects of both atropine and 4 beta-PDB, given in combination, were additive. 6. The net inhibition of the evoked tritium overflow caused by the muscarine receptor agonists carbachol and oxotremorine was similar, irrespective of whether 4 beta-PDB was present or not. 7. Similar results to those for muscarine autoreceptor-mediated inhibition, were obtained for inhibition of the stimulated tritium overflow caused by the adenosine receptor agonist (-)-N6-(R-phenylisopropyl)-adenosine ((-)-PIA) and the opioid receptor agonist ethylketocyclazocine (EKC). The net inhibition of both agonists was independent of the presence of the phorbol ester. 8. The above results provide further evidence for participation of a presynaptically located protein kinase C in the modulation of acetylcholine release. However, the modulatory mechanisms which are coupled to presynaptic receptors and mediate inhibition of release seem not to be directly affected by protein kinase C.
Allgaier
C
C
Institute of Pharmacology, Freiburg i. Br., Federal Republic of Germany.
Daschmann
B
B
Huang
H Y
HY
Hertting
G
G
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005071:Evoked Potentials; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008564:Membrane Potentials; D010703:Phorbol Esters / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D011817:Rabbits
D010703:Phorbol Esters; D001285:Atropine; D002217:Carbachol; D011493:Protein Kinase C; D011112:Polymyxin B; D000109:Acetylcholine