Involvement of protein kinase C activation in regulation of acetylcholine release from rat hippocampal slices by minaprine.
Involvement of protein kinase C (PKC) activation in the regulation of acetylcholine (ACh) release from rat hippocampal slices by minaprine, [3(2-morpholinoethylamino)-4-methyl-6-phenylpyridazine] was investigated. Phorbol esters such as 4 beta-phorbol 12,13-dibutylate (PDBu) and 12-o-tetradecanoylphorbol 13-acetate (TPA) enhanced high K(+)-evoked [3H]ACh release from rat hippocampal slices. The enhancing effect of phorbol ester was attenuated by PKC inhibitors, staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). However, the inactive phorbol analogue, 4 alpha-phorbol 12,13-didecanoate (PDD) had no effect on [3H]ACh release. Minaprine and 4-aminopyridine (4-AP) attenuated the inhibitory effect of 5-hydroxytryptamine (5-HT) on high K(+)-evoked [3H]ACh release from rat hippocampal slices. The attenuating effect of minaprine on the inhibition of [3H]ACh release by 5-HT was prevented by staurosporine, while that of 4-AP was not influenced. Furthermore, PDBu blocked voltage-dependent, rapidly inactivating 42K efflux from rat brain synaptosomes. These results suggest that minaprine attenuates the inhibitory effect of 5-HT on ACh release via PKC activation in rat hippocampus, and that the blockade of the K+ channel with PKC activation might be involved in the action of minaprine.
Chaki
S
S
Department of Pharmacology, Taisho Pharmaceutical Co. Ltd., Saitama, Japan.
Muramatsu
M
M
Otomo
S
S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D019311:Staurosporine; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D007546:Isoquinolines; D010879:Piperazines; D011724:Pyridazines; C006149:minaprine; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015761:4-Aminopyridine; D011493:Protein Kinase C; D019311:Staurosporine; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium