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• W2019646525 endingPage "697" @default.
• W2019646525 startingPage "686" @default.
• W2019646525 abstract "Activation of cAMP-protein kinase A (PKA) is widely reported to facilitate synaptic transmission. Here, we examined the presynaptic loci of PKA action using isolated nerve terminals (synaptosoms). The adenylyl cyclase (AC) activator, forskolin, failed to have any effect on 4-aminopyridine (4-AP)-evoked glutamate release, when added alone. However, in the presence of the alkylxanthine, IBMX, forskolin strongly facilitated glutamate release. This potentiation of release was blocked by the PKA inhibitors Rp-cAMPS and H7. Given that IBMX has dual activity, antagonizing adenosine receptors as well as inhibiting cAMP phosphodiesterase, we examined the effect of a selective adenosine A(1) receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and RO20-1724, a specific phosphodiesterase inhibitor. Both unmasked the forskolin-mediated modulation of glutamate release. Conversely, the adenosine analogue, N(6)-cyclohexyladenosine (CHA), reversed the facilitation induced by forskolin+RO20-1724. Adenosine A(1) receptor activation, therefore, appears to curtail cAMP/PKA-induced potentiation of glutamate release. Looking at the targets for cAMP/PKA-mediated potentiation of glutamate release, while synaptosomal excitability was only marginally increased, basal and 4-AP-evoked-increases in [Ca(2+)](c) were substantially enhanced by forskolin+IBMX. Moreover, glutamate release elicited by Ca(2+)-ionophore (ionomycin)-induced Ca(2+)-entry was facilitated by forskolin+IBMX. cAMP/PKA-mediated facilitation of glutamate release may therefore involve modulation of Ca(2+)-entry, as well as downstream events controlling synaptic vesicle recruitment and exocytosis." @default.
• W2019646525 created "2016-06-24" @default.
• W2019646525 creator A5027845271 @default.
• W2019646525 creator A5031762065 @default.
• W2019646525 date "2003-04-01" @default.
• W2019646525 modified "2023-10-01" @default.
• W2019646525 title "Opposing facilitatory and inhibitory modulation of glutamate release elicited by cAMP production in cerebrocortical nerve terminals (synaptosomes)" @default.
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• W2019646525 doi "https://doi.org/10.1016/s0028-3908(03)00045-5" @default.
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