Evidence that metabolically active synaptosomes lack functional cyclic AMP-dependent protein kinase.
Cyclic adenosine monophosphate (cAMP)-mediated signal transduction was evaluated in synaptosomes prepared from rat brain cortex. Adenylate cyclase was responsive to known adenylate cyclase stimulators including peptides (CRH and VIP), catecholamines (norepinephrine and isoproterenol) and ligands that directly stimulate adenylate cyclase (forskolin). Cyclic AMP accumulation also increased approximately 2 to 3-fold, but none of the agonists was able significantly to activate cyclic AMP-dependent protein kinase (A-kinase) in cortical synaptosomes. However, in parallel studies with slices prepared from rat brain cortex, adenylate cyclase activity, cAMP accumulation and A-kinase activity were all stimulated by CRH, VIP, norepinephrine, isoproterenol and forskolin. These data suggest that, in intact synaptosomes, either the cellular machinery which facilitates binding of cAMP to the regulatory subunit of A-kinase is missing or the cAMP produced by adenylate cyclase is not accessible to A-kinase.
Dhillon
G S
GS
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Koenig
M L
ML
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013574:Synaptosomes / Q000201:enzymology / Q000378:metabolism*
D047428:Protein Kinase Inhibitors; D003346:Corticotropin-Releasing Hormone; D011494:Protein Kinases; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine