Immunophilin ligands promote penile neurogenesis and erection recovery after cavernous nerve injury

Arthur Burnett, Robyn E. Becker

Research output: Contribution to journalArticle

Abstract

Purpose: We investigated the long-term effect of immunophilin ligands on erection physiology and cavernous tissue histology using rat models of unilateral and bilateral cavernous nerve (CN) injury. Materials and Methods: Adult male Sprague-Dawley rats were administered the immunophilin ligand FK506 (5 mg/kg subcutaneously daily for 5 days), the nonimmunosuppressant FK506 derivative GPI1046 (3 to 3-pyridyl)-1-propyl(2 seconds)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidine carboxylate) (40 mg/kg subcutaneously daily for 5 or 28 days) or saline immediately upon induction of 2 paradigms of cavernous nerve injury, namely focal transection of the CN unilaterally, and a combination of focal transection of the CN unilaterally and excision of a 5 mm segment of contralateral CN (BIL treated). At 28 days following CN injury electrical stimulation of the transected CN and penile erection monitoring were performed. Whole penes were removed and evaluated immunohistochemically for the nitric oxide generator neuronal nitric oxide synthase, the neuronal marker synaptophysin, the endothelial marker CD31 and the smooth muscle marker α-actin. Results: In unilaterally treated groups erection recovery was significantly greater in FK506 treated than in saline treated animals ((83.5% ± 9.2% vs 24.3% ± 8.1%, p <0.001) and similarly greater in GPI1046 treated animals than in the respective saline treated controls for this group (57.9% ± 12.6% vs 23.8% ± 7.0%, p <0.05). In BIL treated groups erection recovery for FK506 and GPI1046 treated rats exceeded saline treated values by approximately 70% (p <0.05) and 40% (p = 0.14), respectively. After 28 days of continuous treatment in BIL treated groups erection recovery for GPI1046 treated rats exceeded saline treated values by 140% (p <0.05). Neuronal and endothelial staining was preserved after immunophilin ligand treatment. Conclusions: Immunophilin ligands exert neurotrophic effects on the penile innervation that preserve cavernous tissue structure and promote erectile function recovery in rats after extensive CN injury.

Original languageEnglish (US)
Pages (from-to)495-500
Number of pages6
JournalJournal of Urology
Volume171
Issue number1
DOIs
StatePublished - Jan 2004

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Immunophilins
Penile Erection
Neurogenesis
Tacrolimus
Ligands
Wounds and Injuries
Nitric Oxide Synthase Type I
Synaptophysin
Recovery of Function
Electric Stimulation
Smooth Muscle
Sprague Dawley Rats
Actins
Histology
Nitric Oxide
Staining and Labeling
Control Groups

Keywords

  • Immunophilins
  • Impotence
  • Nerve regeneration
  • Penis
  • Rats, Sprague-Dawley

ASJC Scopus subject areas

  • Urology

Cite this

Immunophilin ligands promote penile neurogenesis and erection recovery after cavernous nerve injury. / Burnett, Arthur; Becker, Robyn E.

In: Journal of Urology, Vol. 171, No. 1, 01.2004, p. 495-500.

Research output: Contribution to journalArticle

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abstract = "Purpose: We investigated the long-term effect of immunophilin ligands on erection physiology and cavernous tissue histology using rat models of unilateral and bilateral cavernous nerve (CN) injury. Materials and Methods: Adult male Sprague-Dawley rats were administered the immunophilin ligand FK506 (5 mg/kg subcutaneously daily for 5 days), the nonimmunosuppressant FK506 derivative GPI1046 (3 to 3-pyridyl)-1-propyl(2 seconds)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidine carboxylate) (40 mg/kg subcutaneously daily for 5 or 28 days) or saline immediately upon induction of 2 paradigms of cavernous nerve injury, namely focal transection of the CN unilaterally, and a combination of focal transection of the CN unilaterally and excision of a 5 mm segment of contralateral CN (BIL treated). At 28 days following CN injury electrical stimulation of the transected CN and penile erection monitoring were performed. Whole penes were removed and evaluated immunohistochemically for the nitric oxide generator neuronal nitric oxide synthase, the neuronal marker synaptophysin, the endothelial marker CD31 and the smooth muscle marker α-actin. Results: In unilaterally treated groups erection recovery was significantly greater in FK506 treated than in saline treated animals ((83.5{\%} ± 9.2{\%} vs 24.3{\%} ± 8.1{\%}, p <0.001) and similarly greater in GPI1046 treated animals than in the respective saline treated controls for this group (57.9{\%} ± 12.6{\%} vs 23.8{\%} ± 7.0{\%}, p <0.05). In BIL treated groups erection recovery for FK506 and GPI1046 treated rats exceeded saline treated values by approximately 70{\%} (p <0.05) and 40{\%} (p = 0.14), respectively. After 28 days of continuous treatment in BIL treated groups erection recovery for GPI1046 treated rats exceeded saline treated values by 140{\%} (p <0.05). Neuronal and endothelial staining was preserved after immunophilin ligand treatment. Conclusions: Immunophilin ligands exert neurotrophic effects on the penile innervation that preserve cavernous tissue structure and promote erectile function recovery in rats after extensive CN injury.",
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AU - Becker, Robyn E.

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N2 - Purpose: We investigated the long-term effect of immunophilin ligands on erection physiology and cavernous tissue histology using rat models of unilateral and bilateral cavernous nerve (CN) injury. Materials and Methods: Adult male Sprague-Dawley rats were administered the immunophilin ligand FK506 (5 mg/kg subcutaneously daily for 5 days), the nonimmunosuppressant FK506 derivative GPI1046 (3 to 3-pyridyl)-1-propyl(2 seconds)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidine carboxylate) (40 mg/kg subcutaneously daily for 5 or 28 days) or saline immediately upon induction of 2 paradigms of cavernous nerve injury, namely focal transection of the CN unilaterally, and a combination of focal transection of the CN unilaterally and excision of a 5 mm segment of contralateral CN (BIL treated). At 28 days following CN injury electrical stimulation of the transected CN and penile erection monitoring were performed. Whole penes were removed and evaluated immunohistochemically for the nitric oxide generator neuronal nitric oxide synthase, the neuronal marker synaptophysin, the endothelial marker CD31 and the smooth muscle marker α-actin. Results: In unilaterally treated groups erection recovery was significantly greater in FK506 treated than in saline treated animals ((83.5% ± 9.2% vs 24.3% ± 8.1%, p <0.001) and similarly greater in GPI1046 treated animals than in the respective saline treated controls for this group (57.9% ± 12.6% vs 23.8% ± 7.0%, p <0.05). In BIL treated groups erection recovery for FK506 and GPI1046 treated rats exceeded saline treated values by approximately 70% (p <0.05) and 40% (p = 0.14), respectively. After 28 days of continuous treatment in BIL treated groups erection recovery for GPI1046 treated rats exceeded saline treated values by 140% (p <0.05). Neuronal and endothelial staining was preserved after immunophilin ligand treatment. Conclusions: Immunophilin ligands exert neurotrophic effects on the penile innervation that preserve cavernous tissue structure and promote erectile function recovery in rats after extensive CN injury.

AB - Purpose: We investigated the long-term effect of immunophilin ligands on erection physiology and cavernous tissue histology using rat models of unilateral and bilateral cavernous nerve (CN) injury. Materials and Methods: Adult male Sprague-Dawley rats were administered the immunophilin ligand FK506 (5 mg/kg subcutaneously daily for 5 days), the nonimmunosuppressant FK506 derivative GPI1046 (3 to 3-pyridyl)-1-propyl(2 seconds)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidine carboxylate) (40 mg/kg subcutaneously daily for 5 or 28 days) or saline immediately upon induction of 2 paradigms of cavernous nerve injury, namely focal transection of the CN unilaterally, and a combination of focal transection of the CN unilaterally and excision of a 5 mm segment of contralateral CN (BIL treated). At 28 days following CN injury electrical stimulation of the transected CN and penile erection monitoring were performed. Whole penes were removed and evaluated immunohistochemically for the nitric oxide generator neuronal nitric oxide synthase, the neuronal marker synaptophysin, the endothelial marker CD31 and the smooth muscle marker α-actin. Results: In unilaterally treated groups erection recovery was significantly greater in FK506 treated than in saline treated animals ((83.5% ± 9.2% vs 24.3% ± 8.1%, p <0.001) and similarly greater in GPI1046 treated animals than in the respective saline treated controls for this group (57.9% ± 12.6% vs 23.8% ± 7.0%, p <0.05). In BIL treated groups erection recovery for FK506 and GPI1046 treated rats exceeded saline treated values by approximately 70% (p <0.05) and 40% (p = 0.14), respectively. After 28 days of continuous treatment in BIL treated groups erection recovery for GPI1046 treated rats exceeded saline treated values by 140% (p <0.05). Neuronal and endothelial staining was preserved after immunophilin ligand treatment. Conclusions: Immunophilin ligands exert neurotrophic effects on the penile innervation that preserve cavernous tissue structure and promote erectile function recovery in rats after extensive CN injury.

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KW - Impotence

KW - Nerve regeneration

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KW - Rats, Sprague-Dawley

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