The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathway

Nirmala Devi Kanika, Moses T. Tar, Yuehong Tong, Dwaraka Srinivasa Rao Kuppam, Arnold Melman, Kelvin Davies

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume297
Issue number4
DOIs
StatePublished - 2009

Fingerprint

glutaminyl-arginyl-phenylalanyl-seryl-arginine
Priapism
Polyamines
Ornithine Decarboxylase
Arginase
Genes
Plasmids
Up-Regulation
Spermidine Synthase
Adenosylmethionine Decarboxylase
Putrescine
Enzymes
Microarray Analysis

Keywords

  • Erectile
  • Ornithine decarboxylase
  • Polyamine
  • Sialorphin

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathway. / Kanika, Nirmala Devi; Tar, Moses T.; Tong, Yuehong; Kuppam, Dwaraka Srinivasa Rao; Melman, Arnold; Davies, Kelvin.

In: American Journal of Physiology - Cell Physiology, Vol. 297, No. 4, 2009.

Research output: Contribution to journalArticle

@article{c2b3543649684316b0ae226211b91b50,
title = "The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathway",
abstract = "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.",
keywords = "Erectile, Ornithine decarboxylase, Polyamine, Sialorphin",
author = "Kanika, {Nirmala Devi} and Tar, {Moses T.} and Yuehong Tong and Kuppam, {Dwaraka Srinivasa Rao} and Arnold Melman and Kelvin Davies",
year = "2009",
doi = "10.1152/ajpcell.00656.2008",
language = "English (US)",
volume = "297",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathway

AU - Kanika, Nirmala Devi

AU - Tar, Moses T.

AU - Tong, Yuehong

AU - Kuppam, Dwaraka Srinivasa Rao

AU - Melman, Arnold

AU - Davies, Kelvin

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Erectile

KW - Ornithine decarboxylase

KW - Polyamine

KW - Sialorphin

UR - http://www.scopus.com/inward/record.url?scp=70349904712&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349904712&partnerID=8YFLogxK

U2 - 10.1152/ajpcell.00656.2008

DO - 10.1152/ajpcell.00656.2008

M3 - Article

C2 - 19657052

AN - SCOPUS:70349904712

VL - 297

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 4

ER -