Co-activation of PKA and PKC in cerebrocortical nerve terminals synergistically facilitates glutamate release.
Protein kinase A and protein kinase C are involved in processes that enhance glutamate release at glutamatergic nerve terminals. However, it is not known whether these two kinases co-exist within the same nerve terminal, nor is it clear what impact their simultaneous activation may have on neurotransmitter release. In cerebrocortical nerve terminals, co-application of forskolin, which increases cAMP levels and activates protein kinase A, and 4beta-phorbol dibutyrate, a direct activator of protein kinase C, synergistically enhanced the spontaneous release of glutamate. This enhancement exhibited both tetrodotoxin-sensitive and tetrodotoxin-resistant components. Interestingly, the tetrodotoxin-resistant component of release was not observed when cyclic AMP-dependent protein kinase (PKA) and calcium- and phospholipid-dependent protein kinase (PKC) were activated separately, but developed slowly after the co-activation of the two kinases, accounting for 50% of the facilitated release. This release component was dependent on voltage-dependent Ca2+ channels that opened spontaneously after PKA and PKC activation and occurred in the absence of Na+ channel firing. These data provide functional evidence for the co-existence of PKA- and PKC-signalling pathways in a subpopulation of glutamatergic nerve terminals.
Millán
Carmelo
C
Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, Madrid 28040, Spain.
Torres
Magdalena
M
Sánchez-Prieto
José
J
D000818:Animals; D001923:Brain Chemistry; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020536:Enzyme Activators / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D015220:Calcium Channels; D020536:Enzyme Activators; D010703:Phorbol Esters; D005576:Colforsin; D018698:Glutamic Acid; D013779:Tetrodotoxin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C