Phorbol 12,13-dibutyrate enhances electrically stimulated neuromessenger release from rat dorsal hippocampal slices in vitro.
The protein kinase C activator 4 beta-phorbol 12,13-dibutyrate (PDB) enhanced the electrically stimulated release of radiolabelled noradrenaline (NA), acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) from dorsal hippocampal slices of the rat in vitro in a concentration-dependent manner. 4 alpha-Phorbol 12,13 didecanoate did not have an effect on the electrically stimulated release of any of the neuromessengers. Carbachol, which when present in the superfusion medium alone inhibited [14C]ACh release, significantly reduced the effect of PDB on the release of this neuromessenger. In the presence of either clonidine or [Leu5]enkephalin, which by themselves inhibited the electrically stimulated release of [3H]NA, the effect of PDB was significantly reduced. The enhancing effects of yohimbine and PDB on the electrically stimulated release of [3H]NA were additive. In all three cases, thus, the net effects of PDB were of a similar magnitude, whether the various compounds were present or not. Taken together, the present data suggest that the diacylglycerol/protein kinase C pathway is involved in the stimulus-evoked release of NA, ACh and 5-HT from dorsal hippocampal nerve terminals. Protein kinase C seems not to be involved in the modulation of the release of NA via presynaptic alpha 2-adrenoceptors and delta-opioid receptors and in that of ACh via presynaptic ACh receptors in that brain region.
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D004743:Enkephalin, Leucine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D018377:Neurotransmitter Agents; D010703:Phorbol Esters; D015016:Yohimbine; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D004743:Enkephalin, Leucine; D002217:Carbachol; D003000:Clonidine; D000109:Acetylcholine; D009638:Norepinephrine