The opiorphin gene (ProL1) and its homologues function in erectile physiology.
OBJECTIVE
To determine if ProL1, a member of the opiorphin family of genes, can modulate erectile physiology, as it encodes a peptide which acts as a neutral endopeptidase inhibitor, other examples of which (Vcsa1, hSMR3A) modulate erectile physiology.


METHODS
We cloned members of the opiorphin family of genes into the same mammalian expression backbone (pVAX); 100 microg of these plasmids (pVAX-Vcsa1, -hSMR3A, -hSMR3B and -ProL1) were injected intracorporally into retired breeder rats and the affect on erectile physiology assessed visually, by histology and by measuring the intracavernous pressure (ICP) and blood pressure (BP). As a positive control, rats were treated with pVAX-hSlo (expressing the MaxiK potassium channel) and as a negative control the empty backbone plasmid was injected (pVAX). We also compared the level of expression of ProL1 in corporal tissue of patients not reporting erectile dysfunction (ED), ED associated with diabetes and ED not caused by diabetes.


RESULTS
Gene transfer of plasmids expressing all members of the opiorphin family had a similar and significant effect on erectile physiology. At the concentration used in these experiments (100 microg) they resulted in higher resting ICP, and histological and visual analysis showed evidence of a priapic-like condition. After electrostimulation of the cavernous nerve, rats had significantly better ICP/BP than the negative control (pVAX). Gene transfer of pVAX-hSlo increased the ICP/BP ratio to a similar extent to the opiorphin homologues, but with no evidence for a priapic-like condition. Corpora cavernosa tissue samples obtained from men with ED, regardless of underlying causes, had significant down-regulation of both hSMR3A and ProL1.


CONCLUSIONS
All members of the human opiorphin family of genes can potentially modulate erectile physiology. Both hSMR3 and ProL1 are down-regulated in the corpora of men with ED, and therefore both genes can potentially act as markers of ED.
Tong
Yuehong
Y
Department of Urology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
Tar
Moses
M
Melman
Arnold
A
Davies
Kelvin
K
D000818:Animals; D015536:Down-Regulation; D007172:Erectile Dysfunction / Q000235:genetics* / Q000503:physiopathology; D015870:Gene Expression; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000235:genetics* / Q000502:physiology; D010410:Penile Erection / Q000235:genetics / Q000502:physiology*; D011317:Priapism / Q000235:genetics* / Q000503:physiopathology; D011498:Protein Precursors / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012471:Salivary Proteins and Peptides / Q000235:genetics* / Q000502:physiology
D009842:Oligopeptides; D011498:Protein Precursors; D012471:Salivary Proteins and Peptides; C066861:Smr3b protein, rat; C517879:glutaminyl-arginyl-phenylalanyl-seryl-arginine