Carbon monoxide modulates secretion of corticotropin-releasing factor from rat hypothalamic cell cultures

The present study examined the actions of the putative gaseous neurotransmitter carbon monoxide (CO) on secretion of corticotropin-releasing factor (CRF) from cultured primary rat hypothalamic cells. 6 h treatment of cells with 100% gaseous CO, or with the heme analog, hematin (100 microM) which produces CO as a by-product of its metabolism, increased basal secretion of CRF to 207 +/- 8% and 200 +/- 65% of control respectively. Zinc protoporphyrin IX (ZnPPIX) (0.3-100 microM), a selective inhibitor of CO formation, decreased CRF secretion in a dose-dependent manner. The changes in CRF secretion observed with hematin were attenuated during concurrent treatment with ZnPPIX. These studies suggest that basal secretion of CRF in the rat hypothalamus may be regulated by CO.