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Adenosine Deaminase Enzyme Therapy Prevents and Reverses the Heightened Cavernosal Relaxation in Priapism

Authors

  • Jiaming Wen MD,

    1. Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX, USA;
    2. Department of Urology, Third Xiangya Hospital of Central South University, Changsha, Hunan, China;
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  • Xianzhen Jiang MD,

    1. Department of Urology, Third Xiangya Hospital of Central South University, Changsha, Hunan, China;
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  • Yingbo Dai MD, PhD,

    1. Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX, USA;
    2. Department of Urology, Third Xiangya Hospital of Central South University, Changsha, Hunan, China;
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  • Yujin Zhang MD, PhD,

    1. Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX, USA;
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  • Yuxin Tang MD,

    1. Department of Urology, Third Xiangya Hospital of Central South University, Changsha, Hunan, China;
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  • Hong Sun MD,

    1. Department of Otorhinolaryngology, Third Xiangya Hospital of Central South University, Changsha, Hunan, China
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  • Tiejuan Mi MS,

    1. Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX, USA;
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  • Rodney E. Kellems PhD,

    1. Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX, USA;
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  • Michael R. Blackburn PhD,

    1. Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX, USA;
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  • Yang Xia MD, PhD

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX, USA;
      Yang Xia, MD, PhD, Biochemistry and Molecular Biology, University of Texas-Medical School at Houston, 6431 Fannin, MSB 6.200, Houston, 77030 TX, USA. Tel: 713-500-5039; Fax: 713-500-0652; E-mail: yang.xia@uth.tmc.edu
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Yang Xia, MD, PhD, Biochemistry and Molecular Biology, University of Texas-Medical School at Houston, 6431 Fannin, MSB 6.200, Houston, 77030 TX, USA. Tel: 713-500-5039; Fax: 713-500-0652; E-mail: yang.xia@uth.tmc.edu

ABSTRACT

Introduction.  Priapism featured with painful prolonged penile erection is dangerous and commonly seen in sickle cell disease (SCD). The preventive approaches or effective treatment options for the disorder are limited because of poor understanding of its pathogenesis. Recent studies have revealed a novel role of excess adenosine in priapism caused by heightened cavernosal relaxation, and therefore present an intriguing mechanism-based therapeutic possibility.

Aim.  The aim of this study was to determine the therapeutic effects of adenosine deaminase (ADA) enzyme therapy to lower adenosine in priapism.

Methods.  Both ADA-deficient mice and SCD transgenic (Tg) mice display priapism caused by excessive adenosine. Thus, we used these two distinct lines of mouse models of priapism as our investigative tools. Specifically, we treated both of these mice with different dosages of polyethylene glycol–modified ADA (PEG–ADA) to reduce adenosine levels in vivo. At the end points of the experiments, we evaluated the therapeutic effects of PEG–ADA treatment by measuring adenosine levels and monitoring the cavernosal relaxation.

Main Outcome Measures.  Adenosine levels in penile tissues were measured by high-performance liquid chromatography, and cavernosal relaxation was quantified by electrical field stimulation (EFS)-induced corporal cavernosal strip (CCS) assays.

Results.  We found that lowering adenosine levels in penile tissues by PEG–ADA treatment from birth in ADA-deficient mice prevented the increased EFS-induced CCS relaxation associated with priapism. Intriguingly, in both ADA-deficient mice and SCD Tg mice with established priapism, we found that normalization of adenosine levels in penile tissues by PEG–ADA treatment relieved the heightened EFS-induced cavernosal relaxation in priapism.

Conclusions.  Our studies have identified that PEG–ADA is a novel, safe, and mechanism-based drug to prevent and correct excess adenosine-mediated increased cavernosal relaxation seen in two independent priapic animal models, and suggested its therapeutic possibility in men suffering from priapism. Wen J, Jiang X, Dai Y, Zhang Y, Tang Y, Sun H, Mi T, Kellems RE, Blackburn MR, and Xia Y. Adenosine deaminase enzyme therapy prevents and reverses the heightened cavernosal relaxation in priapism. J Sex Med 2010;7:3011–3022.

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