Expression of different phosphodiesterase genes in human cavernous smooth muscle.
OBJECTIVE
Knowledge of intracellular signal propagation in smooth muscle tone regulation is of major importance in the understanding of the physiology of penile erection, and the development of new and selective pharmacological agents for the treatment of related disorders. Since phosphodiesterases (PDE) are key enzymes of the signaling pathway, we elucidate their presence and potential functional relevance in human cavernous tissue.


METHODS
To identify PDE messenger RNA in human cavernous tissue, we constructed primers for 14 published PDE isoforms. Expression of the genes was then analyzed by reverse transcriptase polymerase chain reaction under standard conditions and by subsequent sequencing.


RESULTS
Messenger RNA was detected in human corpus cavernosum for the human phosphodiesterase isoenzymes and isoforms PDE1A, PDE1B, PDE1C, PDE2A, PDE3A, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE7A, PDE8A and PDE9A.


CONCLUSIONS
A total of 13 PDE genes were expressed in human cavernous tissue, indicating a role of these enzymes in penile erection regulation. The intracellular mechanisms of hydrolyzing cyclic adenosine monophosphate and cyclic guanosine monophosphate by PDEs are more complex than assumed previously. These findings open up new possibilities in the development of drugs for the treatment of erectile dysfunction.
Küthe
A
A
Department of Urology, Hannover Medical School and Lower Saxony Institute for Peptide Research, Hannover, Germany.
Wiedenroth
A
A
Mägert
H J
HJ
Uckert
S
S
Forssmann
W G
WG
Stief
C G
CG
Jonas
U
U
D001483:Base Sequence; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D017931:DNA Primers; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000201:enzymology*; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000201:enzymology*; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D017931:DNA Primers; D012333:RNA, Messenger; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP