Subunits of the nitric oxide receptor, soluble guanylyl cyclase, expressed in rat brain

Despite the widespread use of nitric oxide as a signalling molecule in the central nervous system, the molecular makeup of its receptor, soluble guanylyl cyclase (sGC), therein is poorly understood. Accordingly, RT-PCR and in situ hybridization were used to identify sGC subunits expressed in rat brain. In addition to the expected mRNA for alpha1 and beta1 subunits, message for the beta2 subunit was detected in the cerebellum at all developmental stages investigated (1-150 days postnatum). The use of degenerate primers allowed the identification of mRNA coding for the rat alpha2 subunit, which was also expressed at every age studied. All but beta2 were detected by in situ hybridization in the brains of both 8-day-old and adult rats. The distribution patterns indicated that in some areas, e.g. caudate-putamen and nucleus accumbens, sGC probably exists mainly as the alpha1 beta1 heterodimer. In others, e.g. hippocampus and olfactory bulb, alpha2 beta1 is likely to be dominant. In the cerebellum, alpha1 and beta1 message was strong in the Purkinje cell layer but was not confined to Purkinje cells: smaller cells, presumed to be the Bergmann glia, were also labelled. In contrast, alpha2 mRNA was concentrated in cerebellar granule cells. Western blotting indicated an excess of alpha1 over beta1 protein in the cerebellum, the reverse of what was found in the lung. It is concluded that, in molecular terms, sGC is likely to be more complex and exhibit more regional variation in the brain than previously thought. The functional consequences of this heterogeneity require investigation.