Modulation of cGMP accumulation by adenosine A1 receptors at the hippocampus: Influence of cGMP levels and gender

The Role of cGMP on Adenosine A1 Receptor-mediated Inhibition of Synaptic Transmission at the Hippocampus

“…Interestingly, we found that the dampening of the A 1 receptors on synaptic transmission by the NOS inhibitor, L-NAME, was stronger in females than in male rats, suggesting that the NOS-mediated inhibition of synaptic transmission elicited by adenosine A 1 receptor plays a more relevant role in females. This result is in agreement with our recent finding that adenosine A 1 receptor-mediated activation of the NOS/sGC pathway depends on gender, the A 1 effect being stronger in females than in males rats ( Serpa et al, 2014 ). Although the dampening by L-NAME of the A 1 receptor-mediated inhibition of fEPSP was stronger in females, the stimulatory effect of L-NAME alone on fEPSP did not differ across gender, suggesting that while basal NOS activity inhibits synaptic transmission equally in males and females rats, the role of NOS in mediating A 1 receptor inhibition of fEPSP is more relevant in females.…”

“…The main finding in the present work is that the NOS/sGC/PKG pathway plays a role in the adenosine A 1 receptor-mediated inhibition of excitatory synaptic transmission in the hippocampus. This is in accordance with the recent finding that adenosine A 1 receptor activation increases cGMP formation at the hippocampus ( Serpa et al, 2014 ) where cGMP decreases neurotransmitter release ( Nordström and Bartfai, 1981 ).…”

“…The slope of fEPSPs for the last 10 min before application of CPA was taken as 100%, to allow comparison between the effects of CPA in the two conditions. Male and female animals were used and data analyzed separately since we previously found that adenosine A 1 receptor modulation of the NO/cGMP pathway in the hippocampus depended on gender ( Serpa et al, 2014 ). As illustrated in Figure 2 , in the presence of L-NAME (200 μM) the inhibitory action of CPA on fEPSPs was clearly attenuated in slices taken from female rats.…”

“…On the other hand, NO was shown to enhance the inhibitory effect of 2-chloroadenosine (CADO) in synaptic transmission and this effect of NO was blocked by inhibitors of sGC ( Fragata et al, 2006 ). Our group recently observed that activation of the adenosine A 1 receptor increased cGMP levels in the hippocampus ( Serpa et al, 2014 ). However, whether the inhibitory effect of adenosine A 1 receptor on synaptic neurotransmission is mediated by cGMP is yet unknown.…”

Adenosine inhibits human astrocyte proliferation independently of adenosine receptor activation

“…Adenosine plays a regulatory role in the nervous system by decreasing neurotransmitter release and synaptic transmission, including excitatory synaptic transmission (Dias, Rombo, Ribeiro, Henley, & Sebastião, ; Dunwiddie & Hoffer, ; Pinto, Serpa, Sebastião, & Cascalheira, ; Serpa, Ribeiro, & Sebastião, ), protecting against neurotoxic insults (Ribeiro, Sebastião, & Mendonça, ; Serpa, Pinto, Bernardino, & Cascalheira, ) and modulating synaptic plasticity (Dias et al, ; Santschi, Zhang, & Stanton, ). Most of these adenosine actions are mediated by activation of G‐protein‐coupled adenosine receptors located at the extracellular membrane, specifically A 1 , A 2A , A 2B and A 3 receptors (Dias et al, ; Serpa, Sara, Ribeiro, Sebastião, & Cascalheira, ; Serpa, Sebastião, & Cascalheira, ). However, adenosine may play relevant adenosine receptor‐independent functions, such as modulation of epigenetic processes (Boison, Sandau, Ruskin, Kawamura, & Masino, ; Williams‐Karnesky et al, ).…”