Nitric oxide regulates substance P release from rat spinal cord synaptosomes

Area of Science:

• Neuroscience
• Neurochemistry
• Spinal Cord Physiology

Background:

• Nitric oxide (NO) is a signaling molecule implicated in various physiological processes.
• Its role in regulating synaptic transmission in the spinal cord, particularly concerning substance P (SP) and glutamic acid (Glu) release, requires further elucidation.

Purpose of the Study:

• To investigate whether nitric oxide (NO) directly modulates nerve terminals to regulate synaptic transmission in the spinal cord.
• To examine the effects of NO-donors on the release of substance P (SP) and glutamic acid (Glu) from rat spinal cord synaptosomes.

Main Methods:

• Synaptosomes were prepared from the rat spinal cord.
• Superfusion techniques were used to measure basal and evoked release of SP and Glu.
• The effects of NO-donors (sodium nitroprusside, S-nitroso-N-acetyl-penicillamine), cyclic GMP, and cyclic AMP on neurotransmitter release and cyclic GMP levels were assessed.

Main Results:

• Sodium nitroprusside (NP) significantly reduced depolarization-evoked SP release in a concentration-dependent manner, without affecting basal SP or Glu release.
• The inhibitory effect of NP on SP release was mimicked by S-nitroso-N-acetyl-penicillamine and cyclic GMP, but not cyclic AMP.
• NP treatment led to a concentration-dependent increase in cyclic GMP levels within the synaptosomes.

Conclusions:

• Nitric oxide (NO) directly acts on nerve terminals in the spinal cord to regulate synaptic transmission.
• NO inhibits the release of substance P (SP), likely mediated by the activation of guanylate cyclase and subsequent increase in cyclic GMP.
• These findings suggest a potential interaction between glutamatergic and SP-containing nerve terminals in the spinal cord, with NO playing a regulatory role.