Potent and direct presynaptic modulation of glycinergic transmission in rat spinal neurons by atrial natriuretic peptide

• Effect of ANP on glycinergic nerve terminal was examined in spinal neurons.
• ANP decreased spontaneous and evoked glycine release from presynaptic terminal.
• The effects of ANP were not replicated nor occluded by 8Br-cGMP.
• Both ANP and BNP had no effect on evoked glutamatergic EPSCs in CA3 neurons.
• ANP was potent inhibitor of spinal glycine release.

Atrial and brain natriuretic peptides (ANP and BNP) exist in the central nervous system and modulate neuronal function, although the locus of actions and physiological mechanisms are still unclear. In the present study we used rat spinal sacral dorsal commissural nucleus (SDCN) and hippocampal ‘synaptic bouton’ preparations, to record both spontaneous and evoked glycinergic inhibitory postsynaptic currents (sIPSCs and eIPSCs) in SDCN neurons, and the evoked excitatory postsynaptic currents (eEPSCs) in hippocampal CA3 neurons. ANP potently and significantly reduced the sIPSC frequency without affecting the amplitude. ANP also potently reduced the eIPSCs amplitude concurrently increasing the failure rate and the paired pulse ratio response. These ANP actions were blocked by anantin, a specific type A natriuretic peptide receptor (NPR-A) antagonist. The results clearly indicate that ANP acts directly on glycinergic presynaptic nerve terminals to inhibit glycine release via presynaptic NPR-A. The ANP effects were not blocked by the membrane permeable cGMP analog (8Br-cGMP) suggesting a transduction mechanisms not simply related to increasing cGMP levels in nerve terminals. BNP did not affect on glycinergic sIPSCs and eIPSCs. Moreover, both ANP and BNP had no effect on glutamatergic EPSCs in hippocampal CA3 neurons. The results indicate a potent and selective presynaptic inhibitory action of ANP on glycinergic transmission in spinal cord sensory circuits.