cDNA microarray analysis of differentially expressed genes in penile tissue after treatment with tadalafil.
OBJECTIVE
To evaluate differential gene expression in penile tissue after treatment with the phosphodiesterase 5 (PDE5) inhibitor tadalafil, as of the three clinically available PDE5 inhibitors (sildenafil, tadalafil, and vardenafil) used for the treatment of erectile dysfunction (ED), tadalafil has a long half-life and low incidence of side-effects.


METHODS
In all, 32 adult rats were divided into two groups. The control group received 0.5 mL of drinking water alone, while the tadalafil group was treated with tadalafil at a dose of 0.27 mg/kg. At 4 h after treatment with water or tadalafil the rats were killed and the penile tissue was removed. The total RNA was isolated from the penile tissue from both groups and differentially expressed genes were identified by cDNA microarray analysis. To validate the expression data from the microarray analysis, quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry were used.


RESULTS
In all, 153 genes were differentially expressed between the control group and the tadalafil group. We validated the microarray results by quantitative PCR for the insulin-like growth factor binding protein 6 (IGFBP-6) gene and the neuronal calcium sensor 1 (NCS-1) gene, both of which were up-regulated in the tadalafil group, and for the natriuretic peptide receptor 1 (NPR-1) gene that was down-regulated in this group. Immunohistochemistry showed localization of the NCS-1 protein in sinusoid trabeculae of the corpus cavernosum in control and tadalafil-treated rats.


CONCLUSIONS
There was differential expression in 153 genes after tadalafil treatment. Some of these genes such as IGFBP-6, NPR-1 and NCS-1, might result in new targets in the treatment of ED.
Andrade
Enrico
E
Laboratory of Medical Investigation of Department of Urology, University of Sao Paulo, Sao Paulo, Brazil. enricoandrade@uol.com.br
Andrade
Priscila Maria
PM
Borra
Ricardo Carneiro
RC
Claro
Joaquim
J
Srougi
Miguel
M
D000818:Animals; D002243:Carbolines / Q000627:therapeutic use*; D015536:Down-Regulation; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010410:Penile Erection / Q000187:drug effects* / Q000235:genetics; D010413:Penis / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D000068581:Tadalafil
D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D000068581:Tadalafil