INCREASED INDUCIBLE NITRIC-OXIDE SYNTHASE PROTEIN BUT LIMITED NITRIC-OXIDE FORMATION OCCURS IN ASTROCYTES OF THE HPH-1 (TETRAHYDROBIOPTERINDEFICIENT) MOUSE

It has been suggested that decreased tetrahydrobiopterin (BH4) availab ility may be a useful tool for limiting excessive nitric oxide (NO) fo rmation. In order to test this hypothesis we utilised cultured astrocy tes derived from the brain of the hph-1 (BH4 deficient) mouse. In resp onse to treatment with Lipopolysaccharide and interferon-gamma (LPS/ga mma IFN) levels of BH4 doubled in both wild type and hph-1 astrocytes. However, levels of BH4 in hph-1 astrocytes remained only 25% of the w ild type astrocytes. Nitric oxide formation, measured with an NO-elect rode, was 45% less from LPS/gamma IFN stimulated hph-1 astrocytes comp ared with wild type stimulated astrocytes. Ln contrast, iNOS specific activity and iNOS protein were enhanced in hph-1 stimulated astrocytes by 40 and 60%, respectively when compared with wild type. In conclusi on it appears that whilst a decrease in BH4 may limit NO release per s e, the possibility and consequences of long term 'over' induction of i NOS protein requires further consideration. (C) 1998 Elsevier Science B.V. All rights reserved.