Nitric oxide contributes to opioid release from glia during hypoxia

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Neuronal nitric oxide synthase (NOS) activation increases cerebrospinal fluid (CSF) opioid levels during hypoxia in newborn pigs.
• Nitric oxide (NO) and opioids contribute to hypoxic pial artery dilation.
• The in vivo model does not identify the cellular origin of CSF opioids.

Purpose of the Study:

• To determine if NO contributes to opioid release from primary piglet glial cell cultures.
• To investigate the role of hypoxia and NO signaling in opioid release from glia.

Main Methods:

• Primary piglet glial cell cultures were established.
• Cells were treated with sodium nitroprusside (SNP) and 8-Br cGMP to mimic NO signaling.
• Hypoxia was induced (PO2 approximately 15 mmHg).
• Opioid (methionine enkephalin, leucine enkephalin) and cGMP release were measured.
• The NO synthase inhibitor N-nitro-l-arginine was used.

Main Results:

• Glial cells produced more methionine enkephalin than leucine enkephalin basally.
• SNP and 8-Br cGMP significantly increased the release of both methionine enkephalin and leucine enkephalin.
• SNP also increased cGMP release.
• Hypoxia significantly increased the release of both opioids and cGMP.
• N-nitro-l-arginine blocked hypoxia-induced cGMP release.

Conclusions:

• NO/cGMP signaling and hypoxia stimulate opioid release from glial cells.
• Hypoxia induces NO/cGMP release from glia.
• These findings suggest that NO contributes to opioid release from glia during hypoxic conditions.