Regional and age-dependent expression of the nitric oxide receptor, soluble guanylyl cyclase, in the human brain

Nitric oxide (NO), synthesized by neuronal NO synthase (NOS-I), plays essen tial physiological roles in the brain. The major molecular target for NO is soluble guanylyl cyclase (sGC), a heterodimeric hemoprotein composed of a larger alpha and a smaller beta subunit. Both subunits of sGC are needed to generate the second messenger cyclic GMP (cGMP). Here we show using subuni t-specific antibodies and Western blot analysis that sGC alpha (1) and sGCP (1) protein subunits are present in all examined human brain regions. The r elative distribution of the two subunits was similar and also correlated we ll with the known distribution of NOS-I. The highest expression levels of s GC were found in cortex. basal ganglia and the limbic system. These regions display the most prominent biochemical and histological changes during age ing. In cortex, a negative correlation between the amounts of sGC and age w as found, while sex and post-mortem delay time did not affect sGC levels si gnificantly. Our data suggest that sGC alpha (1) and sGC beta (1) subunits are widely distributed in human brain, consistent with a major role in NO s ignaling. Moreover, the NO/cGMP pathway appears to be affected by ageing in the human brain. (C) 2001 Published by Elsevier Science B.V.