Nitric oxide regulates substance P release from rat spinal cord synaptosomes.
In order to determine whether nitric oxide (NO) acts directly upon nerve terminals to regulate the synaptic transmission at the level of spinal cord, effects of NO-donors on release of substance P (SP) and glutamic acid (Glu) were investigated by superfusion of synaptosomes prepared from the rat spinal cord. Basal levels of endogenous SP and Glu release were 5.99 +/- 2.50 fmol/min/mg of protein and 26.2 +/- 4.8 pmol/min/mg of protein, respectively. Exposure to a depolarizing concentration of KCI evoked 2.7- and 3.8-fold increases in SP and Glu release in a calcium-dependent manner, respectively. Sodium nitroprusside (NP) caused a reduction in the depolarization-evoked overflow of SP in a concentration-dependent manner without affecting its basal release, although it failed to affect either basal or evoked release of Glu. The reduction in SP overflow was also observed by the perfusion with S-nitroso-N-acetyl-penicillamine or membrane-permeable cyclic GMP, but not with cyclic AMP. NP caused the concentration-dependent increases in cyclic GMP levels in synaptosomes. Together with reports that excitatory amino acids stimulate NO synthase and release NO in the spinal cord, these data suggest that there may be an interaction between nerve terminals containing Glu and SP, and that NO may directly participate in the regulation of synaptic transmission in SP-containing nerve terminals, which may be mediated through the activation of guanylate cyclase and the increase in cyclic GMP levels.
Kamisaki
Y
Y
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
Nakamoto
K
K
Wada
K
K
Itoh
T
T
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D004594:Electrophysiology; D016166:Free Radical Scavengers / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
D000596:Amino Acids; D016166:Free Radical Scavengers; D009712:Nucleotides, Cyclic; D009599:Nitroprusside; D009569:Nitric Oxide; D013373:Substance P; D006152:Cyclic GMP; D002118:Calcium