Brundege J M, Diao L, Proctor W R, Dunwiddie T V
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
Neuropharmacology. 1997 Sep;36(9):1201-10. doi: 10.1016/s0028-3908(97)00102-0.
Extracellular adenosine 3':5'-cyclic monophosphate (cAMP) is a potential source of the inhibitory neuromodulator adenosine in the brain. Previous work has demonstrated that cAMP, which is formed intracellularly, can be transported into the extracellular space and subsequently catabolized to adenosine. However, the physiological conditions under which cAMP release might lead to adenosine formation and activation of adenosine receptors are not well understood. In this study we demonstrate that superfusion of hippocampal slices with cAMP or forskolin led to the formation of extracellular adenosine which activated adenosine receptors in a manner comparable to that seen with adenosine superfusion. In contrast, application of brief pulses of cAMP onto the cell bodies of CA1 pyramidal neurons failed to produce an adenosine receptor-mediated response, while application of brief pulses of adenosine or AMP elicited significant responses. These data suggest that large, prolonged increases in extracellular cAMP levels can result in the formation of extracellular adenosine and the activation of adenosine receptors, but brief increases in cAMP levels in the vicinity of individual neurons cannot. These findings imply that increases in cAMP levels may lead to relatively slow increases in extracellular adenosine, as opposed to the fast, spatially restricted increases that would occur following the release of other adenine nucleotides.
细胞外3':5'-环磷酸腺苷（cAMP）是大脑中抑制性神经调质腺苷的潜在来源。先前的研究表明，在细胞内形成的cAMP能够转运至细胞外空间，随后分解代谢为腺苷。然而，cAMP释放导致腺苷形成并激活腺苷受体的生理条件仍未完全明确。在本研究中，我们发现用cAMP或福斯可林灌注海马脑片会导致细胞外腺苷的形成，其激活腺苷受体的方式与腺苷灌注时相当。相比之下，将短暂脉冲的cAMP施加于CA1锥体神经元的细胞体未能产生腺苷受体介导的反应，而施加短暂脉冲的腺苷或AMP则引发了显著反应。这些数据表明，细胞外cAMP水平大幅、持续升高可导致细胞外腺苷的形成及腺苷受体的激活，但单个神经元附近的cAMP水平短暂升高则无法做到。这些发现意味着，cAMP水平的升高可能导致细胞外腺苷相对缓慢地增加，这与其他腺嘌呤核苷酸释放后发生的快速、空间受限的增加形成对比。
