Immunohistochemical localization of calmodulin-dependent cyclic phosphodiesterase in the human brain

The amplification of cyclic nucleotide 'second messenger' signals within ne urons is controlled by phosphodiesterases which are responsible for their d egradation. Calmodulin-dependent phosphodiesterase (CaMPDE) is an abundant enzyme in brain which carries out this function. For the first time, we hav e localized CaMPDE in the normal human brain at various ages, using a monoc lonal antibody designated A6. This antibody was generated using standard te chniques, purified, and applied to tissue sections. Autopsy specimens of hu man brain with no neuropathological abnormalities were selected representin g a range of pre- and postnatal ages. Sections of various brain regions wer e evaluated for immunoreactivity, graded as nil, equivocal, or definite. We demonstrated definite CaMPDE immunohistochemical staining in neocortex, es pecially in neurons in layers 2 and 5. There was definite neuronal immunore activity in the hippocampus, and in the subiculum. The striatum had definit e patchy neuronal staining. Definite terminal staining in the globus pallid us externa and substantia nigra pars reticulata outlined resident neurons, interpreted as axonal terminal staining. Cerebellar Purkinje cells showed d efinite immunoreactivity. In the developing brain, definite immunohistochem ical staining was seen in the cerebellar external granular layer. The expre ssion of CaMPDE in specific subsets of neurons suggests they may correlate with cells having dopaminergic innervation and/or high levels of neuronal i ntegration.