Genomic origin and transcriptional regulation of two variants of cGMP-binding cGMP-specific phosphodiesterases

We have reported alternative splice variants of cGMP-binding cCMP-specific phosphodiesterases (PDE5A), i.e. rat PDE5A2, human PDE5A1, canine PDE5A1 an d PDE5A2, which possess distinct N-terminal sequences. In this study, the D NA sequences corresponding to the unique N-terminal portions of PDE5A1 and PDE5A2 were shown to be tandemly located upstream of exons encoding the com mon region of PDE5A in both human and rat PDE5A genes, The presence of huma n PDE5A2 and rat PDE5A1 transcripts in lungs was confirmed by reverse trans criptase-PCR. These results indicated that two variant forms of PDE5A exist in humans, canines and rats. We examined the tissue distribution of the tw o variants of human PDE5A in adult and fetal humans. The patterns of expres sion of the two alternatively spliced transcripts of human PDE5A in human t issues differed. Many putative regulatory elements including cAMP response elements were observed in the 5'-untranslated region and intron of the PDE5 A gene. The levels of the PDE5A transcripts, especially the PDE5A2 transcri pts, were increased by a cAMP analogueue in cultured rat vascular smooth mu scle cells, indicating that the PDE5A2 is an inducible variant of PDE5A in rats.