ISOLATION AND CHARACTERIZATION OF CDNAS ENCODING PDE5A, A HUMAN CGMP-BINDING, CGMP-SPECIFIC 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE

Human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiest erase (PDE5A) cDNAs were isolated. A 3.1-kb composite DNA sequence ass embled from overlapping cDNAs encodes an 875-amino-acid protein with a predicted molecular mass of 100 012 Da (PDE5A1). Extracts prepared fr om yeast expressing human PDE5A1 hydrolyzed cGMP. This activity was in hibited by the selective PDES inhibitors zaprinast and DMPPO, PDE5A mR NA is expressed in aortic smooth muscle cells, heart, placenta, skelet al muscle and pancreas and, to a much lesser extent, in brain, liver a nd lung. A 5'-splice variant, PDE5A2, encodes an 833-amino-acid protei n with eight unique amino acids at the amino terminus. PDE5A maps to c hromosome 4q 25-27. (C) 1998 Elsevier Science B.V. All rights reserved .