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

2001; Wiley; Volume: 13; Issue: 3 Linguagem: Inglês

10.1046/j.1460-9568.2001.01421.x

1460-9568

Barry Gibb, John Garthwaite,

Neuroscience of respiration and sleep

Abstract 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 α1 and β1 subunits, message for the β2 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 α2 subunit, which was also expressed at every age studied. All but β2 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 α1β1 heterodimer. In others, e.g. hippocampus and olfactory bulb, α2β1 is likely to be dominant. In the cerebellum, α1 and β1 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, α2 mRNA was concentrated in cerebellar granule cells. Western blotting indicated an excess of α1 over β1 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.