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Excessive penile norepinephrine level underlies impaired erectile function in adenosine A1 receptor deficient mice.

Abstract

INTRODUCTION
Penile erection is a complex neurovascular physiological event controlled by multiple factors and signaling pathways. A considerable amount of evidence indicates that adenosine plays a significant role in cavernosal smooth muscle relaxation. However, the specific role of adenosine and its receptors in erectile physiology and pathology is not fully understood.
AIM
To determine the role of the adenosine A1 receptor (ADORA1) in penile erection.
METHOD
Adenosine A1 receptor deficient (Adora1-/-) mice and aged-matched wild-type (WT) mice were utilized. We evaluated the in vivo erectile function by measuring the intracavernosal pressure (ICP) in response to cavernous nerve stimulation (CNS). Enzyme-linked immunosorbent assay was used to measure the norepinephrine (NE) plasma concentration in the corpus cavernosum and systemic circulation. We also evaluated the myosin light chain phosphorylation (p-MLC) in penile tissue pre- and post-CNS.
MAIN OUTCOME MEASUREMENT
The main outcome measurement of this research was the evaluation of in vivo erectile response to CNS by measuring the ICP in Adora1-/- mice and WT mice and to identify the localization and specific neuron types of ADORA1 expression by dual immunostaining and immunofluorescence co-localization.
RESULT
In vivo, both the ratio of CNS-induced Maximum ICP to mean arterial pressure and CNS-induced slope in Adora1-/- mice were significantly lower than WT mice. At the cellular level in penile tissue, we determined that ADORA1 was highly abundant in neuronal cells. During penile erection, Adora1-/- mice exhibited a higher level of NE plasma concentration in the penis than WT mice. And WT mice had a significantly greater reduction in p-MLC compared to Adora1-/- mice.
CONCLUSION
Our results show that ADORA1 is enriched on neuron cells where it functions to control NE release. Activation of this receptor during penile erection results in reduced NE release and reduced cavernosal smooth muscle contraction, therefore facilitating penile erection.

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  • Publisher Full Text
  • Authors

    Ning C, Qi L, Wen J, Zhang Y, Zhang W, Wang W, Blackburn M, Kellems R, Xia Y

    Institution

    Xiangya Hospital Central South University, Department of Urology, Hangzhou, China Xiangya Hospital Central South University, Changsha, China.

    Source

    The journal of sexual medicine 9:10 2012 Oct pg 2552-61

    MeSH

    Animals
    Arterial Pressure
    Enzyme-Linked Immunosorbent Assay
    Erectile Dysfunction
    Male
    Mice
    Muscle, Smooth
    Myosin Light Chains
    Norepinephrine
    Penile Erection
    Penis
    Receptor, Adenosine A1

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    22862844