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.