Platelet-derived growth factor regulation of type-5 phosphodiesterase in human and rat penile smooth muscle cells.
BACKGROUND
Relaxation of cavernous smooth muscle cells (SMCs) is a key component in the control of the erectile mechanism. SMCs can switch their phenotype from a contractile differentiated state to a proliferative and dedifferentiated state in response to a change of local environmental stimuli. Proliferation and contraction are both regulated by the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are degraded by phosphodiesterases (PDEs). The most abundant PDE present in corpora cavernosa is the electrolytic cGMP-specific phosphodiesterase type 5 (PDE5).


OBJECTIVE
We investigated the cellular localization of PDE5 in in vitro cultured corpora cavernosa cells and the effect of mitogenic stimulation on PDE5 expression.


METHODS
Biochemical ad molecular techniques on cultured SMCs from human and rat penis.


METHODS
We studied the ability of the quiescent SMC phenotype vs. the proliferating phenotype in modulation of PDE5 expression.


RESULTS
We demonstrated that PDE5 is localized in the cytoplasm, in the perinuclear area, and in discrete cytoplasmic foci. As previously demonstrated in human myometrial cells, the cytoplasmic foci may correspond to centrosomes. In corpora cavernosa, PDE5 protein levels are strongly regulated by the mitotic activity of the SMCs, as they were increased in quiescent cultures. In contrast, treatment with platelet-derived grow factor (PDGF), one of the most powerful mitogenic factors for SMCs, reduces the expression of PDE5 after 24 hours of treatment.


CONCLUSIONS
We found that PDGF treatment downregulates PDE5 expression in proliferating SMCs, suggesting that PDE5 may represent one of the markers of the contractile phenotype of the SMCs of corpora cavernosa.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Eleonora
E
Carosa
Alessandra
A
Castri
Chiara
C
Forcella
Guido
G
Sebastiani
Stefania
S
Di Sante
Giovanni L
GL
Gravina
Piero
P
Ronchi
Valeriana
V
Cesarini
Susanna
S
Dolci
Savino
S
Di Stasi
Andrea
A
Lenzi
Emmanuele A
EA
Jannini
D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000201:enzymology*; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000187:drug effects / Q000201:enzymology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017208:Rats, Wistar
D015415:Biomarkers; D010982:Platelet-Derived Growth Factor; D000242:Cyclic AMP; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP
Cavernosal Smooth Muscle Cells; Cell Proliferation; Corpora Cavernosa; Phosphodiesterases; Platelet-Derived Growth Factor; Type-5 Phosphodiesterase