The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathway.
Intracorporal injection of plasmids encoding opiorphins into retired breeder rats can result in animals developing a priapic-like condition. Microarray analysis demonstrated that following intracorporal gene transfer of plasmids expressing opiorphins the most significantly upregulated gene in corporal tissue was the ornithine decarboxylase gene (ODC). Quantitative RT-PCR confirmed the upregulation of ODC, as well as other genes involved in polyamine synthesis, such as arginase-I and -II, polyamine oxidase, spermidine synthase, spermidine acetyltransferase (SAT), and S-adenosylmethionine decarboxylase. Western blot analysis demonstrated upregulation of arginase-I and -II, ODC, and SAT at the protein level. Levels of the polyamine putrescine were upregulated in animals treated with opiorphin-expressing plasmids compared with controls. A direct role for the upregulation of polyamine synthesis in the development of the priapic-like condition was supported by the observation that the ODC inhibitor 1,3-diaminopropane, when added to the drinking water of animals treated with plasmids expressing opiorphins, prevented experimental priapism. We also demonstrate that in sickle cell mice, another model of priapism, there is increased expression of the mouse opiorphin homologue in corporal tissue compared with the background strain at a life stage prior to evidence of priapism. At a life stage when there is onset of priapism, there is increased expression of the enzymes involved in polyamine synthesis (ODC and arginase-I and -II). Our results suggest that the upregulation of enzymes involved in the polyamine synthetic pathway may play a role in the development of experimental priapism and represent a target for the prevention of priapism.
Kanika
Nirmala Devi
ND
Department of Urology and Institute of Smooth Muscle Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Tar
Moses
M
Tong
Yuehong
Y
Kuppam
Dwaraka Srinivasa Rao
DS
Melman
Arnold
A
Davies
Kelvin Paul
KP
D000755:Anemia, Sickle Cell / Q000378:metabolism; D000818:Animals; D001119:Arginase / Q000378:metabolism; D003959:Diamines / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000235:genetics* / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D011317:Priapism / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012471:Salivary Proteins and Peptides / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D000097667:Polyamine Oxidase
D001119:Arginase; D003959:Diamines; D009842:Oligopeptides; D009955:Ornithine Decarboxylase; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D011700:Putrescine; D012471:Salivary Proteins and Peptides; D000097667:Polyamine Oxidase; C517879:glutaminyl-arginyl-phenylalanyl-seryl-arginine; C009475:trimethylenediamine