Effects of substances affecting protein kinase C on histamine-evoked stimulation of cyclic AMP formation in chick cerebral cortex.
In membrane preparation of chick cerebral cortex, HA (histamine) did not affect both basal and forskolin-stimulated adenylyl cyclase activity. However, in slices of chick cerebral cortex prelabeled with [3H]adenine, HA, as well as 2-methylHA, 4-methylHA, and N alpha-methylHA, potently increased [3H]cyclic AMP accumulation in a concentration-dependent manner. The stimulatory effect of the HA-ergic compounds on cyclic AMP formation was antagonized by HA H2-receptor blockers (aminopotentidine, ranitidine), and by chelerythrine (50 microM), a potent and selective inhibitor of PKC (protein kinase C). Of the two other tested PKC inhibitors H-7 (100 microM) significantly reduced the HA action, while the effect of staurosporine (1 microM) did not reach the level of statistical significance. Preincubation of chick cerebral cortical slices with a PKC activator, PDB (4 beta-phorbol 12,13-dibutyrate, 1 microM), markedly enhanced the accumulation of cyclic AMP evoked by HA, 2-methylHA, 4-methylHA and N alpha-methylHA. 4 beta-Phorbol, inactive on PKC, was ineffective. A possible role of PKC in the regulation of HA-induced cyclic AMP synthesis in chick cerebrum has been discussed.
Zawilska
J B
JB
Department of Biogenic Amines, Polish Academy of Sciences, Lódź, Poland.
Kołodziejczyk
M
M
Nowak
J Z
JZ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000633:toxicity; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D002273:Carcinogens / Q000633:toxicity; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002645:Chickens; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity; D006146:Guanidines / Q000633:toxicity; D006632:Histamine / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000633:toxicity; D008297:Male; D010617:Phenanthridines / Q000633:toxicity; D015240:Phorbol 12,13-Dibutyrate / Q000633:toxicity; D010880:Piperidines / Q000633:toxicity; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011899:Ranitidine / Q000633:toxicity; D019311:Staurosporine / Q000633:toxicity
D000470:Alkaloids; D053119:Benzophenanthridines; D002273:Carcinogens; D004791:Enzyme Inhibitors; D006146:Guanidines; D006635:Histamine H2 Antagonists; D010617:Phenanthridines; D010880:Piperidines; C103275:aminopotentidine; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D006632:Histamine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011899:Ranitidine; D000242:Cyclic AMP; C016299:chelerythrine; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D019311:Staurosporine; D000225:Adenine