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K. Tsuda, S. Tsuda, I. Nishio, Y. Masuyama, P-544: Role of cyclic adenosine monophosphate-dependent protein kinase (PKA) in the regulation of acetylcholine release in the central nervous system in hypertension, American Journal of Hypertension, Volume 14, Issue S1, April 2001, Page 213A, https://doi.org/10.1016/S0895-7061(01)01840-4
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Abstract
Recent studies have provided evidence showing that the central cholinergic nervous system may actively participate in blood pressure control and other cardiovascular regulations. The present study was undertaken to investigate the role of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) in the regulation of acetylcholine (ACh) release in the central nervous system in hypertension. (1) In an in vitro study, exogenously applied dopamine (DA) and D2-receptor agonist apomorphine that are thought to reduce intracellular cAMP content via the Gi-proteins significantly inhibited the stimulation-evoked ACh release in rat striatal slices (fractional release ratio at 1 Hz electrical stimulation: control 0.855±0.021, mean±SEM, n=6, apomorphine 10-7 mol/L 0.292±0.017, n=6, P<0.05). (2) An increase in extracellular DA by the DA uptake-blocker GBR-12909 suppressed the release of ACh. (3) The PKA inhibitor, H-8, also inhibited the stimulation-evoked ACh release. In addition, the inhibitory effect of H-8 on the stimulation-evoked ACh release was significantly greater in spontaneously hypertensive rats (SHR) than in normotensive controls (fractional release ratio in the presence of 10-5 mol/L of H-8: SHR 0.810±0.006, n=6, NT 0.932±0.037, n=6, P<0.05). The results of the present study showed that cAMP and PKA might be involved in the mechanisms of ACh release in the central nervous system. Furthermore, the greater effect of H-8 in SHR suggests that the enhanced PKA activity might have a crucial role in the regulation of choloinergic nervous activity in the central nervous system in hypertension.
