title: A detailed study on the effects of protein kinase C activation on alpha-2 adrenoceptor-coupled modulation of norepinephrine release in hippocampus.
abstract: The question was studied whether there is a direct link between protein kinase C and presynaptic alpha-2 adrenoceptors regulating depolarization-induced norepinephrine (NE) release. Effects of the protein kinase C activator 4 beta-phorbol 12,13-dibutyrate (4 beta-PDB) on electrically evoked [3H]NE release were investigated in rabbit and rat hippocampus. Release evoked with 4 pulses/100 Hz (POP stimulation; i.e. under conditions virtually free of autoinhibition), was increased by 4 beta-PDB in a comparable manner in both species. Conversely, the alpha-2 adrenoceptor agonist clonidine diminished POP-induced [3H]NE release in a concentration-dependent manner. The net effects of clonidine were of a similar magnitude up to near maximal concentrations, irrespective of whether or not the 4 beta-PDB was present. Correspondingly, the net effect of 4 beta-PDB remained unchanged under these conditions. An impairment of the net effect of 4 beta-PDB was only seen at higher concentrations of clonidine. Concurrent addition of the alpha-2 adrenoceptor antagonist yohimbine and 4 beta-PDB enhanced release elicited with 36 pulses/3 Hz (i.e., in presence of autoinhibition), in a manner which was at least additive. Taken together, the above data exclude a direct link between presynaptic alpha-2 adrenoceptors and protein kinase C and restrict a functional interaction to very distinctive conditions.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Freiburg, F.R.G.
authors.forename: C
authors.initials: C
authors.lastname: Allgaier
authors.forename: G
authors.initials: G
authors.lastname: Hertting
authors.forename: E A
authors.initials: EA
authors.lastname: Singer
mesh_terms: D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism
chemical_list: D011942:Receptors, Adrenergic, alpha; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D003000:Clonidine; D009638:Norepinephrine