Nitric oxide contributes to opioid release from glia during hypoxia.
Activation of neuronal nitric oxide (NO) synthase contributes to increased CSF concentrations of the opioids methionine enkephalin and leucine enkephalin during hypoxia in the newborn pig. NO and these opioids, in turn, contribute to hypoxic pial artery dilation. However, the cellular site of origin for opioids detected in CSF cannot be determined using this in vivo model. The present study, therefore, was designed to determine if NO contributes to opioid release from piglet glia grown in primary culture. Glial cell cultures produced more methionine enkephalin than leucine enkephalin under basal conditions. Administration of SNP and 8-Br cGMP to glial cells increased release of both opioids (471+/-58 vs. 1181+/-148 pg/mg protein methionine enkephalin before and after SNP 10-6 M). SNP also increased release of cGMP. Exposure of piglet glial cells to lower than normal O2 increased the release of both opioids (503+/-61 vs. 1488+/-186 pg/mg protein methionine enkephalin before and after hypoxia, (PO2 approximately 15 mmHg). Hypoxia also increased the release of cGMP from glia while the NO synthase inhibitor N-nitro-l-arginine blocked that release. These data show that NO/cGMP and hypoxia release opioids from glia. Additionally, hypoxia releases NO/cGMP from glia. These data therefore suggest that NO contributes to opioid release from glia during hypoxia.
Armstead
W M
WM
Departments of Anesthesia and Pharmacology, University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D006152:Cyclic GMP / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013552:Swine
D013439:Sulfhydryl Reagents; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D006152:Cyclic GMP