IMMUNOLOGICAL ASSESSMENT OF THE DISTRIBUTION OF TYPE-VII ADENYLYL-CYCLASE IN BRAIN

The localization of the nine identified isoforms of adenylyl cyclase i n brain has been largely based on determination of patterns of mRNA ex pression. A polyclonal antibody has now been developed that specifical ly recognizes Type VII adenylyl cyclase. This antibody was used for im munocytochemical analysis of the distribution of Type VII adenylyl cyc lase in rat brain. Labeling of Type VII adenylyl cyclase was observed in several areas, including cerebellum, caudate-putamen, nucleus accum bens, hippocampus and cerebral cortex. In some of these areas, the sta ining of the adenylyl cyclase protein suggested the possibility of pre synaptic localization. For example, in situ hybridization showed Type VII adenylyl cyclase mRNA concentrated in cerebellar granule neurons. The cerebellar granule cell layer, however, showed little immunostaini ng, while punctate immunostaining was observed in the molecular layer. These results suggested that protein synthesized in the granule neuro ns may be targeted to the neuron terminals. Punctate staining in the c audate-putamen, globus pallidus and nucleus accumbens also suggested t he possibility of axonal and/or dendritic localization of Type VII ade nylyl cyclase in these regions. Labeling of the soma of cerebellar Pur kinje cells, cortical pyramidal and non-pyramidal cells and interneuro ns in the cerebellum and hippocampus was also observed. Type VII adeny lyl cyclase, like the other adenylyl cyclase isoforms, has distinct re gulatory characteristics, including sensitivity to stimulation by G(s) alpha and G protein beta gamma subunits, modulation by protein kinase C, and high sensitivity to stimulation by ethanol. These characterist ics, and the discrete localization of this enzyme, may contribute to i ts ability to provide signal integration and/or control of neurotransm itter release in particular neurons or brain areas. (C) 1998 Elsevier Science B.V.