title: Excessive penile norepinephrine level underlies impaired erectile function in adenosine A1 receptor deficient mice.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To determine the role of the adenosine A1 receptor (ADORA1) in penile erection.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Xiangya Hospital Central South University, Department of Urology, Hangzhou, China Xiangya Hospital Central South University, Changsha, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Ning
authors.forename: Lin
authors.initials: L
authors.lastname: Qi
authors.forename: Jiaming
authors.initials: J
authors.lastname: Wen
authors.forename: Yujin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weiru
authors.initials: W
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Blackburn
authors.forename: Rodney
authors.initials: R
authors.lastname: Kellems
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D004797:Enzyme-Linked Immunosorbent Assay; D007172:Erectile Dysfunction / Q000378:metabolism*; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000378:metabolism* / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010410:Penile Erection / Q000502:physiology*; D010413:Penis / Q000378:metabolism / Q000503:physiopathology*; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018994:Myosin Light Chains; D043682:Receptor, Adenosine A1; D009638:Norepinephrine