NITRIC-OXIDE CONTRIBUTES TO OPIOID RELEASE FROM GLIA DURING HYPOXIA

Activation of neuronal nitric oxide (NO) synthase contributes to incre ased CSF concentrations of the opioids methionine enkephalin and leuci ne enkephalin during hypoxia in the newborn pig. NO and these opioids, in rum, contribute to hypoxic pial artery dilation. However, the cell ular site of origin for opioids detected in CSF cannot be determined u sing 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 enkep halin than leucine enkephalin under basal conditions. Administration o f SNP and 8-Br cCMP 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 O-2 increased the release of both opioids (503 +/- 61 vs. 1488 +/- 186 pg/mg protein methionine enkephalin before and after hypoxia, (P-O2 approximate to 15 mmHg). Hy poxia also increased the release of cGMP from glia while the NO syntha se inhibitor N-nitro-L-arginine blocked that release. These data show that NO/cGMP and hypoxia release opioids rom glia. Additionally, hypox ia releases NO/cGMP from glia. These data therefore suggest that NO co ntributes to opioid release from glia during hypoxia. (C) 1998 Elsevie r Science B.V. All rights reserved.