Effects of H-89, an inhibitor of protein kinase A, on the acetylcholine release from myenteric plexus of guinea pig ileum.
In order to clarify the involvement of cyclic AMP-dependent protein kinase (protein kinase A) in acetylcholine (ACh) release from myenteric plexus of guinea pig ileum, the effect of H-89, a specific inhibitor of protein kinase A, on the ACh release was investigated. H-89 (0.1-10 microM) inhibited the spontaneous and nicotine-induced release of ACh in a concentration dependent manner. It at 1 microM decreased both kinds of release of ACh to almost half of the control, but it did not affect the ACh release evoked by electrical field stimulation and by 5-hydroxytryptamine. H-89 had no significant effect on the indomethacin (IND), an inhibitor of PG synthesis, -insensitive component of the spontaneous and nicotine-induced release of, ACh. OP-41483, an analog of PGI2 and forskolin, an activator nicotine-induced release of, ACh. OP-41483, an analog of PGI2 and forskolin, an activator of adenylate cyclase, reversed the inhibitory effect of IND on the ACh release. H-89 at 1 microM completely inhibited the reverse effects of OP-41483 and forskolin. These results suggest that activation of protein kinase A is essential for modulation of the nicotine-induced and spontaneous ACh release from myenteric plexus of guinea pig ileum and the activity of protein kinase A is regulated by endogenous PGs via intracellular cyclic AMP level.
Takeuchi
T
T
Department of Veterinary Pharmacology, College of Agriculture, Osaka Prefecture University, Sakai, Japan.
Fukunaga
Y
Y
Hata
F
F
Yagasaki
O
O
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009197:Myenteric Plexus / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology; D013449:Sulfonamides
D007546:Isoquinolines; D011453:Prostaglandins; D013449:Sulfonamides; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D000109:Acetylcholine