1. Effects of substances affecting protein kinase C on histamine-evoked stimulation of cyclic AMP formation in chick cerebral cortex.
- Author
-
Zawilska JB, Kołodziejczyk M, and Nowak JZ
- Subjects
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine toxicity, Adenine analogs & derivatives, Adenine pharmacology, Adenylyl Cyclases metabolism, Alkaloids, Animals, Benzophenanthridines, Carcinogens toxicity, Cerebral Cortex enzymology, Cerebral Cortex metabolism, Chickens, Colforsin pharmacology, Dose-Response Relationship, Drug, Enzyme Activation drug effects, Enzyme Inhibitors toxicity, Guanidines toxicity, Histamine H2 Antagonists toxicity, Male, Phenanthridines toxicity, Phorbol 12,13-Dibutyrate toxicity, Piperidines toxicity, Ranitidine toxicity, Staurosporine toxicity, Cerebral Cortex drug effects, Cyclic AMP biosynthesis, Histamine pharmacology, Protein Kinase C antagonists & inhibitors
- Abstract
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.
- Published
- 1996