Potent and direct presynaptic modulation of glycinergic transmission in rat spinal neurons by atrial natriuretic peptide.
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.
Research Division for Life Science, Kumamoto Health Science University, 325 Izumi-machi, Kita-ku, Kumamoto 861-5598, Japan.
Megumi
M
Maeda
Yuji
Y
Mizuno
Masahito
M
Wakita
Toshitaka
T
Yamaga
Kiku
K
Nonaka
Min-Chul
MC
Shin
Kiyomitsu
K
Shoudai
Norio
N
Akaike
D015761:4-Aminopyridine / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005998:Glycine / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology*; D013873:Thionucleotides / Q000494:pharmacology
D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D010456:Peptides, Cyclic; D026902:Potassium Channel Blockers; D013873:Thionucleotides; C472610:atrial natriuretic peptide, rat; C068090:anantin; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; C012647:QX-314; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D009320:Atrial Natriuretic Factor; D008012:Lidocaine; D015761:4-Aminopyridine; D006152:Cyclic GMP; D005998:Glycine
ANP; Glycinergic transmission; Rat spinal neuron; Spontaneous and evoked IPSC; ‘Synaptic bouton’ preparation