Expression of cGMP-specific phosphodiesterase 9A mRNA in the rat brain

cGMP has been implicated in the regulation of many essential functions in t he brain, such as synaptic plasticity, phototransduction, olfaction, and be havioral state. Cyclic nucleotide phosphodiesterase (PDE) hydrolysis of cGM P is the major mechanism underlying the clearance of cGMP and is likely to be important in any process that depends on intracellular cGMP. PDE9A has t he highest affinity for cGMP of any PDE, and here we studied the localizati on of this enzyme in the rat brain using in situ hybridization. PDE9A mRNA is widely distributed throughout the brain with varying regional expression . The pattern of PDE9A mRNA expression closely resembles that of soluble gu anylyl cyclase (sGC) in the rat brain, suggesting a possible functional ass ociation or coupling of these two enzymes in the regulation of cGMP levels. Most of the brain areas expressing PDE9A mRNA also contain neuronal nitric oxide synthase (NOS), the enzymatic source of NO and the principal activat or of sGC. PDE9A is the only cGMP-specific PDE with significant expression in the forebrain, and as such is likely to play an important role in NO-cGM P signaling.