Pinto Isa, Serpa André, Sebastião Ana M, Cascalheira José F
CICS-UBI - Health Sciences Research Center, University of Beira Interior Covilhã, Portugal.
Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of LisbonLisboa, Portugal; Institute of Molecular Medicine, University of LisbonLisboa, Portugal.
Front Pharmacol. 2016 Apr 22;7:103. doi: 10.3389/fphar.2016.00103. eCollection 2016.
Both adenosine A1 receptor and cGMP inhibit synaptic transmission at the hippocampus and recently it was found that A1 receptor increased cGMP levels in hippocampus, but the role of cGMP on A1 receptor-mediated inhibition of synaptic transmission remains to be established. In the present work we investigated if blocking the NOS/sGC/cGMP/PKG pathway using nitric oxide synthase (NOS), protein kinase G (PKG), and soluble guanylyl cyclase (sGC) inhibitors modify the A1 receptor effect on synaptic transmission. Neurotransmission was evaluated by measuring the slope of field excitatory postsynaptic potentials (fEPSPs) evoked by electrical stimulation at hippocampal slices. N6-cyclopentyladenosine (CPA, 15 nM), a selective A1 receptor agonist, reversibly decreased the fEPSPs by 54 ± 5%. Incubation of the slices with an inhibitor of NOS (L-NAME, 200 μM) decreased the CPA effect on fEPSPs by 57 ± 9% in female rats. In males, ODQ (10 μM), an sGC inhibitor, decreased the CPA inhibitory effect on fEPSPs by 23 ± 6%, but only when adenosine deaminase (ADA,1 U/ml) was present; similar results were found in females, where ODQ decreased CPA-induced inhibition of fEPSP slope by 23 ± 7%. In male rats, the presence of the PKG inhibitor (KT5823, 1 nM) decreased the CPA effect by 45.0 ± 9%; similar results were obtained in females, where KT5823 caused a 32 ± 9% decrease on the CPA effect. In conclusion, the results suggest that the inhibitory action of adenosine A1 receptors on synaptic transmission at hippocampus is, in part, mediated by the NOS/sGC/cGMP/PKG pathway.
腺苷A1受体和环鸟苷酸（cGMP）均抑制海马体中的突触传递，最近研究发现A1受体可提高海马体中的cGMP水平，但cGMP在A1受体介导的突触传递抑制中所起的作用仍有待确定。在本研究中，我们探究了使用一氧化氮合酶（NOS）、蛋白激酶G（PKG）和可溶性鸟苷酸环化酶（sGC）抑制剂阻断NOS/sGC/cGMP/PKG通路是否会改变A1受体对突触传递的影响。通过测量海马体切片电刺激诱发的场兴奋性突触后电位（fEPSP）斜率来评估神经传递。选择性A1受体激动剂N6-环戊基腺苷（CPA，15 nM）可使fEPSP可逆性降低54±5%。在雌性大鼠中，用NOS抑制剂（L-NAME，200 μM）孵育切片可使CPA对fEPSP的作用降低57±9%。在雄性大鼠中，sGC抑制剂ODQ（10 μM）可使CPA对fEPSP的抑制作用降低23±6%，但仅在存在腺苷脱氨酶（ADA，1 U/ml）时；在雌性大鼠中也发现了类似结果，ODQ可使CPA诱导的fEPSP斜率抑制降低23±7%。在雄性大鼠中，PKG抑制剂（KT5823，1 nM）可使CPA的作用降低45.0±9%；在雌性大鼠中也得到了类似结果，KT5823可使CPA的作用降低32±9%。总之，结果表明腺苷A1受体对海马体突触传递的抑制作用部分是由NOS/sGC/cGMP/PKG通路介导的。
Zotero 插件
